pseudomonas-aeruginosa-induced-lung-injury-model

<em>Pseudomonas aeruginosa</em> Induced Lung Injury Model

In order to study human acute lung injury and pneumonia, it is important to develop animal models to mimic various pathological features of this disease. ...

University of Illinois at Chicago

During the early development of the mouse lung a number of genes encoding signaling molecules are differentially expressed in the epithelium and mesenchyme of the distal buds. Evidence suggests they play a role in regulating the stereotypic processes of bud outgrowth and branching as well as proximal-distal patterning of both cell layers. To better understand the mechanisms underlying branching morphogenesis, a subtractive hybridization and differential screen was carried out for genes preferentially expressed in the epithelium at the tips of embryonic day 11.5 lung buds, versus more proximal regions. Twenty genes were identified, assigned to different categories based on sequence analysis, and their distal expression confirmed by whole-mount in situ hybridization.

Differential gene expression in the distal tip endoderm of the embryonic mouse lung.

During the development of the mouse lung, the expression of a number of genes, including those encoding growth factors and components of their downstream signaling pathways, is enriched in the epithelium and/or mesenchyme of the distal buds. In this location, they regulate processes such as cell proliferation, branching morphogenesis, and the differentiation of specialized cell types. Here, we report that the expression of Pea3 and Erm (or Etv5, Ets variant gene 5), which encode Pea3 subfamily ETS domain transcription factors, is initially restricted to the distal buds of the developing mouse lung. Erm is transcribed exclusively in the epithelium, while Pea3 is expressed in both epithelium and mesenchyme. Erm/Pea3 are downstream of FGF signaling from the mesenchyme, but their responses toward different FGFs are not the same. The functions of the two proteins were investigated by transgenic expression of a repressor form of Erm specifically in the embryonic lung epithelium. When examined at E18.5, the distal epithelium of transgenic lungs is composed predominantly of immature type II cells, while no mature type I cells are observed. In contrast, the differentiation of proximal epithelial cells, including ciliated cells and Clara cells, appears to be unaffected. A model is proposed for the role of Pea3/Erm during the dynamic process of lung bud outgrowth and proximal-distal differentiation, in response to FGF signaling. Our results provide the first functional evidence that Pea3 subfamily members play a role in epithelial-mesenchymal interactions during lung organogenesis.

Role for ETS domain transcription factors Pea3/Erm in mouse lung development.

The development of many organs, including the lung, depends upon a process known as branching morphogenesis, in which a simple epithelial bud gives rise to a complex tree-like system of tubes specialized for the transport of gas or fluids. Previous studies on lung development have highlighted a role for fibroblast growth factors (FGFs), made by the mesodermal cells, in promoting the proliferation, budding, and chemotaxis of the epithelial endoderm. Here, by using a three-dimensional culture system, we provide evidence for a novel role for Netrins, best known as axonal guidance molecules, in modulating the morphogenetic response of lung endoderm to exogenous FGFs. This effect involves inhibition of localized changes in cell shape and phosphorylation of the intracellular mitogen-activated protein kinase(s) (ERK1/2, for extracellular signal-regulated kinase-1 and -2), elicited by exogenous FGFs. The temporal and spatial expression of netrin 1, netrin 4, and Unc5b genes and the localization of Netrin-4 protein in vivo suggest a model in which Netrins in the basal lamina locally modulate and fine-tune the outgrowth and shape of emergent epithelial buds.

Novel role for Netrins in regulating epithelial behavior during lung branching morphogenesis.

Extracellular signal-regulated kinase 8 (ERK8) is the most recently identified member of the ERK subfamily of MAPKs. Although other members of the ERK subfamily are established regulators of signaling pathways involved in cell growth and/or differentiation, less is known about ERK8. To understand the cellular function of ERK8, a yeast two-hybrid screen of a human lung library was performed to identify binding partners. One binding partner identified was Hic-5 (also known as ARA55), a multiple LIM domain containing protein implicated in focal adhesion signaling and the regulation of specific nuclear receptors, including the androgen receptor and the glucocorticoid receptor (GR). Co-immunoprecipitation experiments in mammalian cells confirmed the interaction between Hic-5 and both ERK8 and its rodent ortholog ERK7. The C-terminal region of ERK8 was not required for the interaction. Although the LIM3 and LIM4 domains of Hic-5 were sufficient and required for this interaction, the specific zinc finger motifs in these domains were not. Transcriptional activation reporter assays revealed that ERK8 can negatively regulate transcriptional co-activation of androgen receptor and GRalpha by Hic-5 in a kinase-independent manner. Knockdown of endogenous ERK8 in human airway epithelial cells enhanced dexamethasone-stimulated transcriptional activity of endogenous GR. Transcriptional regulation of GRalpha and interaction with its ligand binding domain by ERK8 were dependent on the presence of Hic-5. These results provide the first physiological function for human ERK8 as a negative regulator of human GRalpha, acting through Hic-5, and suggest a broader role for ERK8 in the regulation of nuclear receptors beyond estrogen receptor alpha.

ERK8 down-regulates transactivation of the glucocorticoid receptor through Hic-5.

To understand how rabies virus (RV) infection results in neuronal dysfunction, the authors employed proteomics technology to profile host responses to RV infection. In mice infected with wild-type (wt) RV, the expression of proteins involved in ion homeostasis was altered. H(+) ATPase and Na(+)/K(+) ATPase were up-regulated whereas Ca(2+) ATPase was down-regulated, which resulted in reduction of the intracellular Na(+) and Ca(2+) concentrations. Furthermore, infection with wt RV resulted in down-regulation of soluble NSF attachment receptor proteins (SNAREs) such as alpha-synaptosome-associated protein (SNAP), tripartite motif-containing 9 (TRIM9), syntaxin, and pallidin, all of which are involved in docking and fusion of synaptic vesicles to and with presynaptic membrane. As a consequence, accumulation of synaptic vesicles was observed in the presynapses of mice infected with wt RV. These data demonstrate that infection with wt RV results in alteration of host protein expression, particularly those involved in ion homeostasis and docking and fusion of synaptic vesicles to presynaptic membrane, which may lead to neuronal dysfunction. On the other hand, attenuated RV up-regulated the expression of proteins involved in the induction of apoptosis, explaining why apoptosis is observed only in cells or animals infected with attenuated RV in previous studies.

Proteomic profiling reveals that rabies virus infection results in differential expression of host proteins involved in ion homeostasis and synaptic physiology in the central nervous system.

In the early stages of lung development, the endoderm undergoes extensive and stereotypic branching morphogenesis. During this process, a simple epithelial bud develops into a complex tree-like system of tubes specialized for the transport and exchange of gas with blood. The endodermal cells in the distal tips of the developing lung express a special set of genes, have a higher proliferation rate than proximal part, undergo shape change and initiate branching morphogenesis. In this study, we found that of the four p38 genes, only p38 alpha mRNA is localized specifically to the distal endoderm suggesting a role in the regulation of budding morphogenesis. Chemical inhibitors specific for the p38 alpha and p38 beta isoforms suppress budding of embryonic mouse lung explants and isolated endoderm in vitro. Specific knockdown of p38 alpha in cultured lung endoderm using shRNA also inhibited budding morphogenesis, consistent with the chemical inhibition of the p38 signaling pathway. Disruption of p38 alpha did not affect proliferation or expression of the distal cell markers, Sox9 and Erm. However, the amount of E-cadherin protein increased significantly and ectopic expression of E-cadherin also impaired budding of endoderm in vitro. These results suggest that p38 alpha modulates epithelial cell-cell interactions and possibly cell rearrangement during branching morphogenesis. This study provides the first evidence that p38 alpha is involved in the morphogenesis of an epithelial organ.

Role for mitogen-activated protein kinase p38 alpha in lung epithelial branching morphogenesis.

Human metapneumovirus (HMPV) has been identified as a worldwide agent of serious upper and lower respiratory tract infections in infants and young children. HMPV is second only to respiratory syncytial virus (RSV) as a leading cause of bronchiolitis, and, like RSV, consists of two major genotypes that cocirculate and vary among communities year to year. Children who have experienced acute HMPV infection may develop sequelae of wheezing and asthma; however, the features contributing to this pathology remain unknown. A possible mechanism for postbronchiolitis disease is that HMPV might persist in the lung providing a stimulus that could contribute to wheezing and asthma. Using immunohistochemistry to identify HMPV-infected cells in the lungs of mice, we show that HMPV mediates biphasic replication in respiratory epithelial cells then infection migrates to neuronal processes that innervate the lungs where the virus persists with no detectable infection in epithelial cells. After glucocorticoid treatment, the virus is reactivated from neural fibers and reinfects epithelial cells. The findings show that HMPV persists in neural fibers and suggest a mechanism for disease chronicity that has important implications for HMPV disease intervention strategies.

Human metapneumovirus establishes persistent infection in the lungs of mice and is reactivated by glucocorticoid treatment.

An efficient multi-frequency extracavity Raman laser for nanosecond pulses was realized by taking advantage of the anisotropic optical property of the KGd(WO4)2 crystal. The conversion efficiencies of the converter were investigated versus the pump pulse energy, pump polarization, and output coupling rate experimentally and theoretically. Based on the coupled radiation transfer equations, a theoretical model was deduced to predict the performance of solid-state extracavity Raman lasers. This model was solved numerically to analyze the operation of the extracavity Raman laser with the KGd(WO4)2 crystal, and the numerical results had a good agreement with the experimental ones.

Theoretical and experimental research on the multi-frequency Raman converter with KGd(WO4)2 crystal.

Tumors depend upon angiogenesis for growth and metastasis. It is therefore critical to understand the inhibitory signaling mechanisms in endothelial cells that control angiogenesis. Epac is a cyclic adenosine 5'-monophosphate-activated guanine nucleotide exchange factor for Rap1. In this study, we show that activation of Epac or Rap1 leads to potent inhibition of angiogenesis in vivo. Epac/Rap1 activation down-regulates inhibitor of differentiation 1 (Id1), which negatively regulates thrombospondin-1 (TSP1), an inhibitor of angiogenesis. Consistent with this mechanism, activation of Epac/Rap 1 induces expression of TSP1; conversely, depletion of Epac reduces TSP1 levels in endothelial cells. Blockade of TSP1 binding to its receptor, CD36, rescues inhibition of chemotaxis or angiogenesis by activated Epac/Rap1. Mitogen-activated protein kinase kinase 5, a downstream mediator of vascular endothelial growth factor, antagonizes the effects of Epac/Rap1 by inducing Id1 and suppressing TSP1 expression. Finally, TSP1 is also secreted by fibroblasts in response to Epac/Rap1 activation. These results identify Epac and Rap1 as inhibitory regulators of the angiogenic process, implicate Id1 and TSP1 as downstream mediators of Epac/Rap1, and highlight a novel interplay between pro- and antiangiogenic signaling cascades involving multiple cell types within the angiogenic microenvironment.

A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis.

The alveolar epithelium is composed of the flat type I cells comprising 95% of the gas-exchange surface area and cuboidal type II cells comprising the rest. Type II cells are described as facultative progenitor cells based on their ability to proliferate and trans-differentiate into type I cells. In this study, we observed that pneumonia induced by intratracheal instillation of Pseudomonas aeruginosa (PA) in mice increased the expression of the forkhead transcription factor FoxM1 in type II cells coincidentally with the induction of alveolar epithelial barrier repair. FoxM1 was preferentially expressed in the Sca-1(+) subpopulation of progenitor type II cells. In mice lacking FoxM1 specifically in type II cells, type II cells showed decreased proliferation and impaired trans-differentiation into type I cells. Lungs of these mice also displayed defective alveolar barrier repair after injury. Expression of FoxM1 in the knockout mouse lungs partially rescued the defective trans-differentiation phenotype. Thus, expression of FoxM1 in type II cells is essential for their proliferation and transition into type I cells and for restoring alveolar barrier homeostasis after PA-induced lung injury.

FoxM1 mediates the progenitor function of type II epithelial cells in repairing alveolar injury induced by Pseudomonas aeruginosa.

Basierend auf Cyanine Dye Sonde OXAZOL gelb (YO) und Cy(3), wurden eine Reihe von neuartigen Styryl Cyanine F&auml;rbungen entwickelt und synthetisiert. Carbazol eingef&uuml;gt wurde, in die Strukturen der YO und Cy(3) als eine Br&uuml;cke, die Benzoxazole und Indol-Gruppe zu verkn&uuml;pfen. Diese &Auml;nderung f&uuml;hrte zu eine neuartige Art von Benzoxazole Indol Styryl Cyanine Dye mit einer Kette Carbazol-gebr&uuml;ckt. Die Farbstoffe waren gekennzeichnet durch (1) HNMR und MS. Die Spektren des Romans, die Farbstoffe auch durchgef&uuml;hrt wurden und die Ergebnisse zeigten, dass die maximale Emissionswellenl&auml;nge von der Carbazol Styryl Cyanine Dye verschobene rot war, die Stokes-Verschiebung erh&ouml;ht und die Fluoreszenz-Intensit&auml;t erh&ouml;ht verglichen mit denen von YO und Cy(3). Diese Ergebnisse zeigten, dass der Roman Farbstoff als eine ausgezeichnete Leuchtstoffpr&uuml;fspitze in biologischen Kennzeichnung eingesetzt werden k&ouml;nnten.

Synthese und Spektren einer Art von Roman l&auml;ngere Wellenl&auml;nge Benzoxazole Indol Styryl Cyanine Dye mit einer Kette Carbazol-gebr&uuml;ckt.

Basato su cianina colorante sonda oxazole giallo (YO) e Cy(3), una serie di coloranti cianina styryl romanzo sono stati progettati e sintetizzati. Carbazolo &egrave; stata inserita nelle strutture di YO e Cy(3) di agire come un ponte per collegare il gruppo benzoxazole e indolo. Questa modifica ha portato un nuovo tipo di benzoxazole indolo styryl cianina colorante con una catena a ponte carbazolo. I coloranti sono stati caratterizzati da (1) HNMR e MS. Gli spettri del romanzo coloranti inoltre sono state eseguite e i risultati hanno mostrato che la lunghezza d&#39;onda massima emissione della tintura carbazolo styryl cianina fu spostato rosso, lo spostamento di Stokes &egrave; aumentato e l&#39;intensit&agrave; di fluorescenza maggiore rispetto a quelli di YO e Cy(3). Questi risultati hanno indicato che il colorante romanzo potrebbe essere utilizzato come un&#39;eccellente sonda fluorescente in etichettatura biologica.

Sintesi e spettri di una sorta di romanzo pi&ugrave; lungo-lunghezza d&#39;onda dell&#39;indolo Benzoxazole Styryl cianina colorante con una catena a ponte carbazolo.

&#x30B7;&#x30A2;&#x30CB;&#x30F3;&#x8272;&#x7D20;&#x30D7;&#x30ED;&#x30FC;&#x30D6; &#x30AA;&#x30AD;&#x30B5;&#x30BE;&#x30FC;&#x30EB;&#x9EC4;&#x8272; (YO) &#x304A;&#x3088;&#x3073; Cy(3) &#x306B;&#x57FA;&#x3065;&#x3044;&#x3066;&#x3001;&#x4E00;&#x9023;&#x306E;&#x5C0F;&#x8AAC;&#x30B9;&#x30C1;&#x30EA;&#x30EB; &#x30B7;&#x30A2;&#x30CB;&#x30F3;&#x8272;&#x7D20;&#x8A2D;&#x8A08;&#x3057;&#x3001;&#x5408;&#x6210;&#x3057;&#x307E;&#x3059;&#x3002;&#x30AB;&#x30EB;&#x30D0;&#x30BE;&#x30FC;&#x30EB;&#x306F;&#x3001;YO &#x3068; Cy(3) &#x30D6;&#x30EA;&#x30C3;&#x30B8;&#x3068;&#x3057;&#x3066;&#x6A5F;&#x80FD;&#x3055;&#x305B;&#x308B;&#x30D9;&#x30F3;&#x30BE;&#x30AA;&#x30AD;&#x30B5;&#x30BE;&#x30FC;&#x30EB;&#x3068;&#x30A4;&#x30F3;&#x30C9;&#x30FC;&#x30EB;&#x306E;&#x30B0;&#x30EB;&#x30FC;&#x30D7;&#x3092;&#x30EA;&#x30F3;&#x30AF;&#x3059;&#x308B;&#x306E;&#x69CB;&#x9020;&#x4F53;&#x306B;&#x633F;&#x5165;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x3053;&#x306E;&#x5909;&#x66F4;&#x306F;&#x30D9;&#x30F3;&#x30BE;&#x30AA;&#x30AD;&#x30B5;&#x30BE;&#x30FC;&#x30EB; &#x30A4;&#x30F3;&#x30C9;&#x30FC;&#x30EB; &#x30B9;&#x30C1;&#x30EA;&#x30EB; &#x30B7;&#x30A2;&#x30CB;&#x30F3;&#x8272;&#x7D20;&#x30AB;&#x30EB;&#x30D0;&#x30BE;&#x30FC;&#x30EB;&#x67B6;&#x6A4B;&#x30C1;&#x30A7;&#x30FC;&#x30F3;&#x4ED8;&#x304D;&#x306E;&#x5C0F;&#x8AAC;&#x4E00;&#x7A2E;&#x3067;&#x8D77;&#x56E0;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x67D3;&#x6599;&#x306F;&#x3001;(1) HNMR &#x3068; MS &#x306B;&#x3088;&#x3063;&#x3066;&#x7279;&#x5FB4;&#x3065;&#x3051;&#x3089;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x5F37;&#x5316;&#x3055;&#x308C;&#x305F;&#x86CD;&#x5149;&#x5F37;&#x5EA6;&#x5897;&#x52A0;&#x30B9;&#x30C8;&#x30FC;&#x30AF;&#x30B9; &#x30B7;&#x30D5;&#x30C8;&#x3068;&#x30AB;&#x30EB;&#x30D0;&#x30BE;&#x30FC;&#x30EB; &#x30B9;&#x30C1;&#x30EA;&#x30EB; &#x30B7;&#x30A2;&#x30CB;&#x30F3;&#x8272;&#x7D20;&#x306E;&#x6700;&#x5927;&#x767A;&#x5149;&#x6CE2;&#x9577;&#x30B7;&#x30D5;&#x30C8;&#x306E;&#x8D64;&#x3092;&#x793A;&#x3057;&#x305F;&#x7D50;&#x679C;&#x67D3;&#x6599;&#x3082;&#x884C;&#x3063;&#x305F;&#x5C0F;&#x8AAC;&#x306E;&#x30B9;&#x30DA;&#x30AF;&#x30C8;&#x30EB; &#x30FB; &#x30E8;&#x3068; Cy(3) &#x306E;&#x3082;&#x306E;&#x3068;&#x6BD4;&#x8F03;&#x3002;&#x751F;&#x7269;&#x5B66;&#x7684;&#x30E9;&#x30D9;&#x30EB;&#x4ED8;&#x3051;&#x3067;&#x3001;&#x512A;&#x79C0;&#x306A;&#x86CD;&#x5149;&#x30D7;&#x30ED;&#x30FC;&#x30D6;&#x3068;&#x3057;&#x3066;&#x65B0;&#x898F;&#x8272;&#x7D20;&#x3092;&#x4F7F;&#x7528;&#x3067;&#x304D;&#x308B;&#x3053;&#x3068;&#x304C;&#x793A;&#x5506;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;

&#x5408;&#x6210;&#x3068;&#x30B9;&#x30DA;&#x30AF;&#x30C8;&#x30EB;&#x5C0F;&#x8AAC;&#x3088;&#x308A;&#x9577;&#x3044;&#x6CE2;&#x9577;&#x30D9;&#x30F3;&#x30BE;&#x30AA;&#x30AD;&#x30B5;&#x30BE;&#x30FC;&#x30EB; &#x30A4;&#x30F3;&#x30C9;&#x30FC;&#x30EB; &#x30B9;&#x30C1;&#x30EA;&#x30EB; &#x30B7;&#x30A2;&#x30CB;&#x30F3;&#x8272;&#x7D20;&#x30AB;&#x30EB;&#x30D0;&#x30BE;&#x30FC;&#x30EB;&#x67B6;&#x6A4B;&#x30C1;&#x30A7;&#x30FC;&#x30F3;&#x4ED8;&#x304D;&#x306E;&#x4E00;&#x7A2E;&#x3002;

&#x57FA;&#x4E8E;&#x5641;&#x83C1;&#x67D3;&#x6599;&#x63A2;&#x9488;&#x5511;&#x9EC4;&#x8272; (YO) &#x548C; Cy(3)&#xFF0C;&#x4E00;&#x7CFB;&#x5217;&#x7684;&#x65B0;&#x578B;&#x82EF;&#x4E59;&#x70EF;&#x83C1;&#x67D3;&#x6599;&#x662F;&#x8BBE;&#x8BA1;&#x548C;&#x5408;&#x6210;&#x3002;&#x5494;&#x5511;&#x63D2;&#x5165;&#x4E86; YO &#x548C; Cy(3) &#x4F5C;&#x4E3A;&#x4E00;&#x5EA7;&#x6865;&#x8981;&#x94FE;&#x63A5;&#x7684;&#x82EF;&#x5E76;&#x5641;&#x5511;&#x548C;&#x5432;&#x54DA;&#x7EC4;&#x7684;&#x7ED3;&#x6784;&#x3002;&#x6B64;&#x4FEE;&#x6539;&#x5BFC;&#x81F4;&#x4E00;&#x79CD;&#x65B0;&#x578B;&#x7684;&#x82EF;&#x5E76;&#x5641;&#x5511;&#x5432;&#x54DA;&#x82EF;&#x4E59;&#x70EF;&#x83C1;&#x67D3;&#x6599;&#x7684;&#x5494;&#x5511;&#x6865;&#x94FE;&#x3002;(1) HNMR &#x548C; MS &#x7684;&#x7279;&#x70B9;&#x662F;&#x67D3;&#x6599;&#x3002;&#x5C0F;&#x8BF4;&#x8FD8;&#x6267;&#x884C;&#x4E86;&#x67D3;&#x6599;&#x7684;&#x5149;&#x8C31;&#x7ED3;&#x679C;&#x663E;&#x793A;&#x5494;&#x5511;&#x82EF;&#x4E59;&#x70EF;&#x83C1;&#x67D3;&#x6599;&#x7684;&#x6700;&#x5927;&#x53D1;&#x5C04;&#x6CE2;&#x957F;&#x662F;&#x8F6C;&#x7684;&#x7EA2;&#xFF0C;&#x589E;&#x52A0;&#x7684;&#x65AF;&#x6258;&#x514B;&#x65AF;&#x8F6C;&#x53D8;&#x548C;&#x589E;&#x5F3A;&#x7684;&#x8367;&#x5149;&#x5F3A;&#x5EA6;&#x4E0E; YO &#x548C; Cy(3) &#x76F8;&#x6BD4;&#x3002;&#x8FD9;&#x4E9B;&#x7ED3;&#x679C;&#x8868;&#x660E;&#x65B0;&#x578B;&#x7684;&#x67D3;&#x6599;&#x53EF;&#x4EE5;&#x7528;&#x4F5C;&#x4F18;&#x79C0;&#x8367;&#x5149;&#x63A2;&#x9488;&#x5728;&#x751F;&#x7269;&#x8367;&#x5149;&#x6807;&#x8BB0;&#x7269;&#x3002;

&#x5408;&#x6210;&#x53CA;&#x5149;&#x8C31;&#x7684;&#x4E00;&#x79CD;&#x65B0;&#x578B;&#x957F;&#x6CE2;&#x957F;&#x82EF;&#x5E76;&#x5641;&#x5511;&#x5432;&#x54DA;&#x82EF;&#x4E59;&#x70EF;&#x83C1;&#x67D3;&#x6599;&#x7684;&#x5494;&#x5511;&#x6865;&#x94FE;&#x3002;

Based on cyanine dye probe oxazole yellow (YO) and Cy(3), a series of novel styryl cyanine dyes were designed and synthesized. Carbazole was inserted into the structures of YO and Cy(3) to act as a bridge to link the benzoxazole and indole group. This modification resulted in a novel kind of benzoxazole indole styryl cyanine dye with a carbazole-bridged chain. The dyes were characterized by (1)HNMR and MS. The spectra of the novel dyes were also performed and the results showed that the maximum emission wavelength of the carbazole styryl cyanine dye was shifted red, the Stokes shift increased and the fluorescence intensity enhanced compared with those of YO and Cy(3). These results indicated that the novel dye could be used as an excellent fluorescent probe in biological labeling.

Synthesis and Spectra of a Kind of Novel Longer-Wavelength Benzoxazole Indole Styryl Cyanine Dye with a Carbazole-Bridged Chain.

Selon cyanine colorant sonde oxazole jaune (YO) et Cy(3), une s&eacute;rie de roman styryl cyanine colorants ont &eacute;t&eacute; con&ccedil;us et synth&eacute;tis&eacute;s. Carbazole a &eacute;t&eacute; ins&eacute;r&eacute;e dans les structures de YO et Cy(3) d&#39;agir comme un pont pour relier le groupe benzoxazole et indole. Cette modification a entra&icirc;n&eacute; une sorte de roman de benzoxazole indole styryl cyanine teinture avec une cha&icirc;ne de carbazole pont&eacute;. Les colorants ont &eacute;t&eacute; caract&eacute;ris&eacute;s par HNMR (1) et MS. Les spectres du roman colorants ont aussi &eacute;t&eacute; r&eacute;alis&eacute;es et les r&eacute;sultats ont montr&eacute; que la longueur d&#39;onde d&#39;&eacute;mission maximale du colorant cyanine carbazole styryl &eacute;tait rouge d&eacute;cal&eacute;, le d&eacute;placement de Stokes a augment&eacute; et l&#39;intensit&eacute; de fluorescence accrue comparativement &agrave; ceux de YO et Cy(3). Ces r&eacute;sultats indiquent que le colorant roman pourrait &ecirc;tre utilis&eacute; comme une sonde fluorescente excellente dans l&#39;&eacute;tiquetage biologique.

La synth&egrave;se et les spectres d&#39;une sorte de roman plus longues longueurs d&#39;onde Benzoxazole Indole Styryl Cyanine teinture avec une cha&icirc;ne de Carbazole pont&eacute;.

Cyanine &#xC5FC;&#xB8CC; &#xD504;&#xB85C;&#xBE0C; oxazole &#xC610;&#xB85C;&#xC6B0; (YO)&#xC640; cy(3)&#xB97C; &#xBC14;&#xD0D5;&#xC73C;&#xB85C;, &#xC18C;&#xC124; styryl cyanine &#xC5FC;&#xB8CC;&#xC758; &#xC2DC;&#xB9AC;&#xC988; &#xC124;&#xACC4; &#xD558; &#xACE0; &#xD569;&#xC131;. Carbazole &#xC694;&#xC640; Cy(3) benzoxazole &#xBC0F; indole &#xADF8;&#xB8F9; &#xC5F0;&#xACB0; &#xB2E4;&#xB9AC; &#xC5ED;&#xD560;&#xC758; &#xAD6C;&#xC870;&#xC5D0; &#xC0BD;&#xC785; &#xD588;&#xB2E4;. &#xC774; &#xC218;&#xC815; benzoxazole indole styryl cyanine &#xC5FC;&#xB8CC; carbazole &#xBE0C;&#xB9AC;&#xC9C0; &#xCCB4;&#xC778;&#xC758; &#xC18C;&#xC124; &#xC885;&#xB958; &#xADC0;&#xCC29;&#xB418; &#xC5C8; &#xB2E4;. &#xC5FC;&#xB8CC; (1) HNMR &#xBC0F; MS&#xC5D0; &#xC758;&#xD574; &#xD2B9;&#xC9D5; &#xD588;&#xB2E4;. &#xC5FC;&#xB8CC;&#xB97C; &#xC218;&#xD589;&#xD55C; &#xB610;&#xD55C; &#xC18C;&#xC124;&#xC758; &#xC2A4;&#xD399;&#xD2B8;&#xB7FC; &#xBC0F; carbazole styryl cyanine &#xC5FC;&#xB8CC;&#xC758; &#xCD5C;&#xB300; &#xBC29;&#xCD9C; &#xD30C;&#xC7A5; &#xC774;&#xB3D9;&#xD55C; &#xB808;&#xB4DC;&#xB294; &#xBCF4;&#xC5EC;&#xC900; &#xACB0;&#xACFC;, &#xC99D;&#xAC00; &#xC2A4;&#xD1A1; &#xAD50;&#xB300; &#xBC0F; &#xD5A5;&#xC0C1; &#xB41C; &#xD615;&#xAD11; &#xAC15;&#xB3C4; &#xC694;&#xC640; cy(3)&#xC758; &#xBE44;&#xAD50;. &#xC774;&#xB7EC;&#xD55C; &#xACB0;&#xACFC; &#xC18C;&#xC124; &#xC5FC;&#xB8CC; &#xC0DD;&#xBB3C; &#xD559;&#xC801; &#xB77C;&#xBCA8;&#xC5D0; &#xB6F0;&#xC5B4;&#xB09C; &#xD615;&#xAD11; &#xD504;&#xB85C;&#xBE0C;&#xB85C; &#xC0AC;&#xC6A9; &#xB420; &#xC218; &#xD45C;&#xC2DC;.

&#xD569;&#xC131; &#xBC0F; Carbazole &#xBE0C;&#xB9AC;&#xC9C0; &#xCCB4;&#xC778; &#xC18C;&#xC124;&#xC744; &#xB354; &#xAE34; &#xD30C;&#xC7A5; Benzoxazole Indole Styryl Cyanine &#xC5FC;&#xB8CC;&#xC758; &#xC77C;&#xC885;&#xC758; &#xC2A4;&#xD399;&#xD2B8;&#xB7FC;.

Partiendo de Cianina tinte sonda oxazol amarillo (YO) y Cy(3), una serie de styryl novela Cianina tintes fueron dise&ntilde;ados y sintetizados. Carbazol fue insertado en las estructuras del YO y Cy(3) para actuar como un puente para unir el grupo benzoxazole y el indol. Esta modificaci&oacute;n result&oacute; en una especie de novela de benzoxazole indole styryl Cianina tinte con una cadena de Carbazol puenteado. Los tintes se caracterizaron por HNMR (1) y MS. Los espectros de la novela de tintes se realizaron y los resultados mostraron que la longitud de onda de emisi&oacute;n m&aacute;xima de colorante Cianina Carbazol styryl fue cambiado de puesto rojo y el desplazamiento de Stokes aumentada la intensidad de fluorescencia mejorada en comparaci&oacute;n con los del YO y Cy(3). Estos resultados indicaron que el tinte de novela podr&iacute;a ser utilizado como una excelente sonda fluorescente en la etiqueta biol&oacute;gica.

S&iacute;ntesis y los espectros de una especie de novela m&aacute;s larga longitud de onda Benzoxazole indol Cianina Styryl tinte con una cadena de Carbazol puenteado.

The existence and identity of multipotent stem cells in the adult lung is currently highly debated. At present, it remains unclear whether candidate stem/progenitor cells are located in the airways, alveoli, or throughout the epithelial lining of the lung. Here, we introduce a method of airway microdissection, which enabled us to study the progenitor behavior of pulmonary epithelial cells in region-specific contexts. The progenitor characteristics of epithelial cells isolated from the trachea, proximal and distal airways, and lung parenchyme were evaluated in vitro and in vivo. We identified a population of airway-derived basal-like epithelial cells with the potential to self-renew and differentiate into airway and alveolar lineages in culture and in vivo after subcutaneous transplantation. The multipotent candidate progenitors originated from a minor fraction of the airway epithelial cell population characterized by high expression of α6 integrin. Results of the current study provide new insights into the regenerative potential of region-specific integrin α6-positive pulmonary epithelial cells.

Article	Year
Differential gene expression in the distal tip endoderm of the embryonic mouse lung. Gene expression patterns : GEP\| PubMed ID: 12617806	2002
Role for ETS domain transcription factors Pea3/Erm in mouse lung development. Developmental biology\| PubMed ID: 12941618	2003
Novel role for Netrins in regulating epithelial behavior during lung branching morphogenesis. Current biology : CB\| PubMed ID: 15186747	2004
ERK8 down-regulates transactivation of the glucocorticoid receptor through Hic-5. The Journal of biological chemistry\| PubMed ID: 16624805	2006
Proteomic profiling reveals that rabies virus infection results in differential expression of host proteins involved in ion homeostasis and synaptic physiology in the central nervous system. Journal of neurovirology\| PubMed ID: 17505979	2007
Role for mitogen-activated protein kinase p38 alpha in lung epithelial branching morphogenesis. Developmental biology\| PubMed ID: 18177852	2008
Human metapneumovirus establishes persistent infection in the lungs of mice and is reactivated by glucocorticoid treatment. Journal of virology\| PubMed ID: 19357175	2009
Theoretical and experimental research on the multi-frequency Raman converter with KGd(WO4)2 crystal. Optics express\| PubMed ID: 19503226	2005
A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis. Blood\| PubMed ID: 19710505	2009
FoxM1 mediates the progenitor function of type II epithelial cells in repairing alveolar injury induced by Pseudomonas aeruginosa. The Journal of experimental medicine\| PubMed ID: 21708928	2011
Synthesis and Spectra of a Kind of Novel Longer-Wavelength Benzoxazole Indole Styryl Cyanine Dye with a Carbazole-Bridged Chain. Journal of fluorescence\| PubMed ID: 23054303	2012
Behavioral Heterogeneity of Adult Mouse Lung Epithelial Progenitor Cells. Stem cells and development\| PubMed ID: 24950291	2014

Yuru Liu

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