a-murine-model-arterial-restenosis-technical-aspects-femoral-wire

A Murine Model of Arterial Restenosis: Technical Aspects of Femoral Wire Injury

Cardiovascular disease caused by atherosclerosis is the leading cause of death in the developed world. Narrowing of the vessel lumen, due to ...

University of Wisconsin School of Medicine and Public Health

MIST1 is a transcription factor expressed in pancreatic acinar cells and other serous exocrine cells. Mice harboring a targeted deletion of the Mist1 gene (Mist1(-/-)) exhibit alterations in acinar regulated exocytosis and aberrant Ca(2+) signaling that are normally controlled by acinar cell Ca(2+)-ATPases. Previous studies indicated that total sarcoendoplasmic reticulum Ca(2+)-ATPases (SERCA) and plasma membrane Ca(2+)-ATPases (PMCA) remained unaffected in Mist1(-/-) acinar cultures. Therefore, we have assessed the expression of Atp2c2, the gene that encodes the secretory pathway Ca(2+)-ATPase 2 (SPCA2). We revealed a dramatic decrease in pancreatic expression of Atp2a2 mRNA and SPCA2 protein in Mist1(-/-) mice. Surprisingly, this analysis indicated that the acinar-specific Atp2c2 mRNA is a novel transcript, consisting of only the 3' end of the gene and the protein and localizes to the endoplasmic reticulum. Expression of SPCA2 was also lost in Mist1(-/-) secretory cells of the salivary glands and seminal vesicles, suggesting that Atp2c2 transcription is regulated by MIST1. Indeed, inducible MIST1 expression in Mist1(-/-) pancreatic acinar cells restored normal Atp2c2 expression, supporting a role for MIST1 in regulating the Atp2c2 gene. Based on these results, we have identified a new Atp2c2 transcript, the loss of which may be linked to the Mist1(-/-) phenotype.

MIST1 regulates the pancreatic acinar cell expression of Atp2c2, the gene encoding secretory pathway calcium ATPase 2.

Endocytic &#xC5B4;&#xB311;&#xD130;&#xC758; epsin &#xAC00;&#xC871; &#xC554;; upregulated&#xB85C; &#xBC1C;&#xACAC; &#xB418;&#xC5C8;&#xC2B5;&#xB2C8;&#xB2E4;. &#xADF8;&#xB7EC;&#xB098; &#xBCD1; &#xC801;&#xC778; &#xC870;&#xAC74;&#xC5D0; &#xC774;&#xB7EC;&#xD55C; &#xC5F0;&#xAD6C; &#xACB0;&#xACFC;&#xC758; &#xAD00;&#xB828;&#xC131;&#xC740; &#xBD88;&#xBD84;&#xBA85;. &#xC6B0;&#xB9AC;&#xB294; &#xCD5C;&#xADFC;&#xC5D0; epsins&#xB294; &#xC140; &#xB9C8;&#xC774;&#xADF8;&#xB808;&#xC774;&#xC158;&#xC5D0; &#xD544;&#xC694;&#xD55C; &#xC99D;&#xBA85; &#xD558;&#xACE0;&#xC788;&#xB2E4;. &#xC0AC;&#xC2E4;, epsin overexpression &#xC554; &#xC138;&#xD3EC; &#xCE68;&#xACF5;&#xC744; &#xCD09;&#xC9C4;&#xD569;&#xB2C8;&#xB2E4;. &#xB610;&#xD55C;, &#xADF8;&#xB9AC;&#xACE0; &#xC6B0;&#xB9AC;&#xC758; &#xC774;&#xC804; &#xC5F0;&#xAD6C; &#xACB0;&#xACFC;&#xC640; &#xB610;&#xD55C; &#xADF8; overexpression epsins &#xC2DD;&#xBBFC;&#xC9C0; &#xACBD;&#xACC4;&#xB97C; &#xB118;&#xC5B4; &#xC0C1;&#xD53C; &#xC138;&#xD3EC; &#xB9C8;&#xC774;&#xADF8;&#xB808;&#xC774;&#xC158;&#xC5D0;&#xC758; &#xAD00;&#xCC30; &#xD569;&#xB2C8;&#xB2E4;. &#xB610;&#xD55C;, &#xC6B0;&#xB9AC;&#xC758; &#xACB0;&#xACFC; epsin-3&#xC740; &#xC140; &#xB9C8;&#xC774;&#xADF8;&#xB808;&#xC774;&#xC158; &#xBC0F; &#xCE68;&#xB7B5;&#xC744; &#xAC15;&#xD654; &#xD558;&#xB294; &#xAC00;&#xC7A5; &#xAC15;&#xB825;&#xD55C; paralog &#xD45C;&#xC2DC; &#xB429;&#xB2C8;&#xB2E4;. &#xD765;&#xBBF8;&#xB86D;&#xAC8C;&#xB3C4;, epsin-3 &#xC2DD; &#xAD11;&#xBC94;&#xC704; &#xD558; &#xAC8C; &#xD558;&#xC9C0;&#xB9CC; &#xB192;&#xC740; &#xC81C;&#xD55C; &#xCCA0;&#xC0C8; keratinocytes &#xBC0F; &#xC801;&#xADF9;&#xC801;&#xC778; carcinomas &#xD558;&#xC9C0; &#xC54A;&#xC2B5;&#xB2C8;&#xB2E4;. &#xCD94;&#xAC00; &#xC870;&#xC0AC; &#xB418; &#xBA74; &#xC6B0;&#xB9AC; &#xB610;&#xD55C; &#xCDCC;&#xC7A5;&#xC554; &#xC138;&#xD3EC;&#xC5D0; &#xD45C;&#xD604; &#xB418; &#xACE0;&#xB85C; epsin-3 &#xC2DD;&#xBCC4; &#xB429;&#xB2C8;&#xB2E4;. &#xC774;&#xB7EC;&#xD55C; &#xC5F0;&#xAD6C; &#xACB0;&#xACFC; &#xAC83;&#xC774; &#xC88B;&#xC2B5;&#xB2C8;&#xB2E4; &#xADF8; upregulation&#xB294; epn3&#xC758; &#xC720;&#xC804;&#xC790;&#xB294; &#xD2B9;&#xD788; &#xCE68;&#xB7B5; &#xC801;&#xC778;, &#xACF5;&#xACA9;&#xC801;&#xC778; &#xC554;&#xACFC; &#xAD00;&#xB828; &#xB41C;. &#xC6B0;&#xB9AC;&#xAC00; &#xC608;&#xCE21; &#xC870;&#xC0AC; endocytic &#xAE30;&#xACC4; &#xBC0F; &#xBA54;&#xCEE4;&#xB2C8;&#xC998; &#xC885;&#xC591; &#xBCF4;&#xAE09;&#xC5D0; &#xAD00;&#xB828; &#xB41C; &#xC0AC;&#xC774; &#xC774;&#xB7EC;&#xD55C; &#xB9C1;&#xD06C;&#xC758; &#xC18C;&#xC124; anti-metastatic &#xBC0F; &#xD56D; &#xC554; &#xC804;&#xB7B5;&#xC758; &#xAC1C;&#xBC1C;&#xC5D0; &#xAE30;&#xC5EC;&#xD560; &#xAC83;&#xC785;&#xB2C8;&#xB2E4;.

Epsins&#39; &#xC554; &#xC138;&#xD3EC; &#xCE68;&#xACF5; &#xC18C;&#xC124; &#xC5ED;&#xD560;&#xC785;&#xB2C8;&#xB2E4;.

La famiglia epsin endocitico adattatori &egrave; stata trovata per essere sovraregolato in cancro; Tuttavia la rilevanza di queste scoperte di questa condizione patologica &egrave; chiara. Abbiamo recentemente dimostrato che epsins sono necessari per la migrazione delle cellule. Infatti, la sovraespressione epsin promuove invasione delle cellule di cancro. Ulteriormente e in accordo con i nostri risultati precedenti, abbiamo anche osservato che sovraespressione di epsins ha portato alla migrazione delle cellule epiteliali, oltre i confini della Colonia. Inoltre, i nostri risultati mostrano che epsin-3 &egrave; il pi&ugrave; potente paralog migliorando invasione e migrazione cellulare. &Egrave; interessante notare che, espressione epsin-3 non &egrave; diffusa ma altamente limitato ai cheratinociti migratori e carcinomi aggressivi. Dopo ulteriori indagini, abbiamo individuato anche epsin-3 come &egrave; espresso nelle cellule di cancro al pancreas. Questi risultati suggeriscono che sovraregolazione del EPN3 gene &egrave; specificamente associati con tumori invasivi, aggressivi. Prevediamo che inchiesta di questi collegamenti tra le macchine endocitico e meccanismi coinvolti nella diffusione tumorale contribuir&agrave; allo sviluppo di nuove strategie di anti-metastatic e anti-cancro.

Ruolo dei Epsins romanzo nell&#39;invasione delle cellule di cancro.

&#x30A8;&#x30F3;&#x30C9;&#x30B5;&#x30A4;&#x30C8;&#x30FC;&#x30B7;&#x30B9;&#x30A2;&#x30C0;&#x30D7;&#x30BF;&#x306E;epsin&#x30D5;&#x30A1;&#x30DF;&#x30EA;&#x30FC;&#x306F;&#x764C;&#x3067;&#x30A2;&#x30C3;&#x30D7;&#x30EC;&#x30AE;&#x30E5;&#x30EC;&#x30FC;&#x30C8;&#x3055;&#x308C;&#x308B;&#x3053;&#x3068;&#x304C;&#x767A;&#x898B;&#x3055;&#x308C;&#x305F;&#x3002;&#x3057;&#x304B;&#x3057;&#x3001;&#x3053;&#x306E;&#x75C5;&#x614B;&#x306B;&#x3053;&#x308C;&#x3089;&#x306E;&#x77E5;&#x898B;&#x306E;&#x59A5;&#x5F53;&#x6027;&#x306F;&#x4E0D;&#x660E;&#x3067;&#x3042;&#x308B;&#x3002;&#x6211;&#x3005;&#x306F;&#x6700;&#x8FD1;&#x3001;epsins&#x304C;&#x7D30;&#x80DE;&#x904A;&#x8D70;&#x306B;&#x5FC5;&#x8981;&#x3068;&#x3055;&#x308C;&#x308B;&#x3053;&#x3068;&#x3092;&#x660E;&#x3089;&#x304B;&#x306B;&#x3057;&#x305F;&#x3002;&#x5B9F;&#x969B;&#x306B;&#x306F;&#x3001;epsin&#x306E;&#x904E;&#x5270;&#x767A;&#x73FE;&#x306F;&#x764C;&#x7D30;&#x80DE;&#x306E;&#x6D78;&#x6F64;&#x3092;&#x4FC3;&#x9032;&#x3057;&#x307E;&#x3059;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;&#x6211;&#x3005;&#x306E;&#x3053;&#x308C;&#x307E;&#x3067;&#x306E;&#x77E5;&#x898B;&#x3068;&#x4E00;&#x81F4;&#x3057;&#x3066;&#x3001;&#x6211;&#x3005;&#x306F;&#x307E;&#x305F;&#x3001;&#x690D;&#x6C11;&#x5730;&#x306E;&#x5883;&#x754C;&#x3092;&#x8D85;&#x3048;&#x3066;&#x4E0A;&#x76AE;&#x7D30;&#x80DE;&#x306E;&#x79FB;&#x884C;&#x306B;&#x3064;&#x306A;&#x304C;&#x3063;epsins&#x306E;&#x904E;&#x5270;&#x767A;&#x73FE;&#x3092;&#x89B3;&#x5BDF;&#x3057;&#x305F;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;&#x6211;&#x3005;&#x306E;&#x7D50;&#x679C;&#x306F;epsin-3&#x306F;&#x6700;&#x3082;&#x5F37;&#x529B;&#x306A;&#x30D1;&#x30E9;&#x30ED;&#x30B0;&#x306E;&#x5F37;&#x5316;&#x7D30;&#x80DE;&#x306E;&#x904A;&#x8D70;&#x304A;&#x3088;&#x3073;&#x6D78;&#x6F64;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;&#x8208;&#x5473;&#x6DF1;&#x3044;&#x3053;&#x3068;&#x306B;&#x3001;epsin-3&#x306E;&#x767A;&#x73FE;&#x306F;&#x3001;&#x5E83;&#x7BC4;&#x56F2;&#x3067;&#x306F;&#x3042;&#x308A;&#x307E;&#x305B;&#x3093;&#x304C;&#x3001;&#x9AD8;&#x5EA6;&#x56DE;&#x904A;&#x6027;&#x30B1;&#x30E9;&#x30C1;&#x30CE;&#x30B5;&#x30A4;&#x30C8;&#x304A;&#x3088;&#x3073;&#x7A4D;&#x6975;&#x7684;&#x306A;&#x764C;&#x306B;&#x5236;&#x9650;&#x3055;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3055;&#x3089;&#x306B;&#x8ABF;&#x67FB;&#x306E;&#x7D50;&#x679C;&#x3001;&#x6211;&#x3005;&#x306F;&#x307E;&#x305F;&#x3001;&#x81B5;&#x81D3;&#x764C;&#x7D30;&#x80DE;&#x3067;&#x767A;&#x73FE;&#x3055;&#x308C;&#x3066;&#x3044;&#x308B;&#x3082;&#x306E;&#x3068;&#x3057;&#x3066;epsin-3&#x3092;&#x540C;&#x5B9A;&#x3057;&#x305F;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x77E5;&#x898B;&#x306F;&#x3001;EPN3&#x907A;&#x4F1D;&#x5B50;&#x306E;&#x30A2;&#x30C3;&#x30D7;&#x30EC;&#x30AE;&#x30E5;&#x30EC;&#x30FC;&#x30B7;&#x30E7;&#x30F3;&#x306F;&#x3001;&#x7279;&#x306B;&#x4FB5;&#x8972;&#x7684;&#x306A;&#x3001;&#x7A4D;&#x6975;&#x7684;&#x306A;&#x764C;&#x306B;&#x95A2;&#x9023;&#x4ED8;&#x3051;&#x3089;&#x308C;&#x3066;&#x3044;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;&#x65B0;&#x898F;&#x6297;&#x8EE2;&#x79FB;&#x304A;&#x3088;&#x3073;&#x6297;&#x764C;&#x6226;&#x7565;&#x306E;&#x958B;&#x767A;&#x306B;&#x8CA2;&#x732E;&#x3057;&#x3066;&#x3044;&#x304D;&#x307E;&#x3059;&#x6211;&#x3005;&#x306F;&#x3001;&#x816B;&#x760D;&#x306E;&#x666E;&#x53CA;&#x306B;&#x95A2;&#x4E0E;&#x3057;&#x3066;&#x30A8;&#x30F3;&#x30C9;&#x30B5;&#x30A4;&#x30C8;&#x30FC;&#x30B7;&#x30B9;&#x306E;&#x6A5F;&#x68B0;&#x3068;&#x6A5F;&#x69CB;&#x306E;&#x9593;&#x306B;&#x3053;&#x308C;&#x3089;&#x306E;&#x30EA;&#x30F3;&#x30AF;&#x306E;&#x305D;&#x306E;&#x8ABF;&#x67FB;&#x3092;&#x4E88;&#x6E2C;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;

&#x764C;&#x7D30;&#x80DE;&#x306E;&#x6D78;&#x6F64;&#x306B;&#x304A;&#x3051;&#x308B;Epsins &#x26;quot;&#x65B0;&#x305F;&#x306A;&#x5F79;&#x5272;

Epsin &#x5BB6;&#x5EAD;&#x7684;&#x541E;&#x9002;&#x914D;&#x5668;&#x5DF2;&#x8BA4;&#x5B9A;&#x4E3A;&#x4EE5;&#x589E;&#x9AD8;&#x764C;&#x75C7; &#xFF1B;&#x4F46;&#x662F;&#x8FD9;&#x4E9B;&#x8C03;&#x67E5;&#x7ED3;&#x679C;&#x5BF9;&#x6B64;&#x75C5;&#x7406;&#x6761;&#x4EF6;&#x7684;&#x76F8;&#x5173;&#x6027;&#x662F;&#x4E0D;&#x6E05;&#x695A;&#x3002;&#x6211;&#x4EEC;&#x6700;&#x8FD1;&#x8868;&#x660E; epsins &#x6240;&#x9700;&#x7684;&#x7EC6;&#x80DE;&#x8FC1;&#x79FB;&#x3002;&#x4E8B;&#x5B9E;&#x4E0A;&#xFF0C;epsin &#x8FC7;&#x5EA6;&#x8868;&#x8FBE;&#x4FC3;&#x8FDB;&#x80BF;&#x7624;&#x7EC6;&#x80DE;&#x4FB5;&#x88AD;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x4E0E;&#x6211;&#x4EEC;&#x4EE5;&#x5F80;&#x7684;&#x8C03;&#x67E5;&#x7ED3;&#x679C;&#xFF0C;&#x6211;&#x4EEC;&#x8FD8;&#x6CE8;&#x610F;&#x5230;&#x8BE5;&#x8868;&#x8FBE;&#x7684; epsins &#x5BFC;&#x81F4;&#x4E0A;&#x76AE;&#x7EC6;&#x80DE;&#x8FC1;&#x79FB;&#x5230;&#x6B96;&#x6C11;&#x5730;&#x8FB9;&#x754C;&#x4E4B;&#x5916;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x6211;&#x4EEC;&#x7684;&#x7814;&#x7A76;&#x7ED3;&#x679C;&#x663E;&#x793A;&#xFF0C;epsin-3 &#x662F;&#x6700;&#x6709;&#x529B;&#x7684; paralog &#x589E;&#x5F3A;&#x7EC6;&#x80DE;&#x8FC1;&#x79FB;&#x548C;&#x4FB5;&#x88AD;&#x3002;&#x6709;&#x8DA3;&#x7684;&#x662F;&#xFF0C;epsin-3 &#x8868;&#x8FBE;&#x5F0F;&#x4E0D;&#x662F;&#x666E;&#x904D;&#x73B0;&#x8C61;&#xFF0C;&#x4F46;&#x9AD8;&#x5EA6;&#x9650;&#x5236;&#x5728;&#x6D04;&#x6E38;&#x7684;&#x89D2;&#x8D28;&#x5F62;&#x6210;&#x7EC6;&#x80DE;&#x548C;&#x4FB5;&#x7565;&#x6027;&#x764C;&#x3002;&#x7ECF;&#x8FDB;&#x4E00;&#x6B65;&#x8C03;&#x67E5;&#xFF0C;&#x6211;&#x4EEC;&#x8FD8;&#x786E;&#x5B9A;&#x4E86; epsin-3 &#x4F5C;&#x4E3A;&#x5728;&#x80F0;&#x817A;&#x764C;&#x7EC6;&#x80DE;&#x4E2D;&#x8868;&#x8FBE;&#x3002;&#x8FD9;&#x4E9B;&#x7814;&#x7A76;&#x7ED3;&#x679C;&#x8868;&#x660E;&#xFF0C;&#x4E0A;&#x8C03;&#x7684; EPN3 &#x57FA;&#x56E0;&#x662F;&#x7279;&#x522B;&#x4E0E;&#x4FB5;&#x88AD;&#x6027;&#x3001; &#x4FB5;&#x7565;&#x6027;&#x7684;&#x764C;&#x75C7;&#x3002;&#x6211;&#x4EEC;&#x9884;&#x6D4B;&#x8C03;&#x67E5;&#x8FD9;&#x4E9B;&#x541E;&#x673A;&#x68B0;&#x548C;&#x53C2;&#x4E0E;&#x80BF;&#x7624;&#x4F20;&#x64AD;&#x7684;&#x673A;&#x5236;&#x4E4B;&#x95F4;&#x7684;&#x94FE;&#x63A5;&#x5C06;&#x4E3A;&#x65B0;&#x578B;&#x6297;&#x548C;&#x6297;&#x764C;&#x6218;&#x7565;&#x7684;&#x53D1;&#x5C55;&#x4F5C;&#x51FA;&#x8D21;&#x732E;&#x3002;

Epsins &#x7684;&#x65B0;&#x578B;&#x80BF;&#x7624;&#x7EC6;&#x80DE;&#x4FB5;&#x88AD;&#x7684;&#x4F5C;&#x7528;&#x3002;

The epsin family of endocytic adaptors has been found to be upregulated in cancer; however the relevance of these findings to this pathological condition is unclear. We have recently demonstrated that epsins are required for cell migration. In fact, epsin overexpression promotes cancer cell invasion. Further, and in agreement with our previous findings, we also observed that overexpression of epsins led to epithelial cell migration beyond colony boundaries. Additionally, our results show that epsin-3 is the most potent paralog enhancing cell migration and invasion. Interestingly, epsin-3 expression is not widespread but highly restricted to migratory keratinocytes and aggressive carcinomas. Upon further investigation, we also identified epsin-3 as being expressed in pancreatic cancer cells. These findings suggest that upregulation of the EPN3 gene is specifically associated with invasive, aggressive cancers. We predict that investigation of these links between the endocytic machinery and mechanisms involved in tumor dissemination will contribute to the development of novel anti-metastatic and anti-cancer strategies.

Epsins' novel role in cancer cell invasion.

La famille d&#x26;#39;adaptateurs epsin endocytose a &#xE9;t&#xE9; trouv&#xE9; &#xE0; une r&#xE9;gulation positive dans le cancer, mais la pertinence de ces conclusions &#xE0; cet &#xE9;tat pathologique n&#x26;#39;est pas claire. Nous avons r&#xE9;cemment d&#xE9;montr&#xE9; que epsins sont n&#xE9;cessaires pour la migration des cellules. En fait, la surexpression epsin favorise l&#x26;#39;invasion des cellules canc&#xE9;reuses. En outre, et en accord avec nos r&#xE9;sultats pr&#xE9;c&#xE9;dents, nous avons &#xE9;galement observ&#xE9; que la surexpression de epsins conduit &#xE0; la migration des cellules &#xE9;pith&#xE9;liales-del&#xE0; des fronti&#xE8;res des colonies. En outre, nos r&#xE9;sultats montrent que epsin-3 est la migration paralogue le plus puissant des cellules am&#xE9;lioration et de l&#x26;#39;invasion. Fait int&#xE9;ressant, epsin-3 &#x26;#39;expression n&#x26;#39;est pas tr&#xE8;s r&#xE9;pandue, mais tr&#xE8;s limit&#xE9; au niveau des k&#xE9;ratinocytes migratoires et des carcinomes agressifs. Apr&#xE8;s une enqu&#xEA;te approfondie, nous avons &#xE9;galement identifi&#xE9; epsin-3 comme &#xE9;tant exprim&#xE9; dans les cellules canc&#xE9;reuses pancr&#xE9;atiques. Ces r&#xE9;sultats sugg&#xE8;rent que la r&#xE9;gulation positive du g&#xE8;ne EPN3 est sp&#xE9;cifiquement associ&#xE9; &#xE0; envahissantes, les cancers agressifs. Nous pr&#xE9;voyons que les enqu&#xEA;tes sur ces liens entre le m&#xE9;canisme d&#x26;#39;endocytose et m&#xE9;canismes impliqu&#xE9;s dans la diss&#xE9;mination tumorale contribuera &#xE0; l&#x26;#39;&#xE9;laboration de nouvelles strat&#xE9;gies anti-m&#xE9;tastatiques et anti-cancer.

Nouveau r&#xF4;le Epsins &#x26;#39;invasion des cellules canc&#xE9;reuses dans

Die Epsin-Familie von endocytic-Adaptern ist gefunden worden, herraufreguliert bei Krebs zu sein; die Relevanz dieser Ergebnisse dieser pathologischen Zustand ist jedoch unklar. Wir haben k&uuml;rzlich bewiesen, dass Epsins f&uuml;r Zelle Migration erforderlich sind. In der Tat f&ouml;rdert Epsin &Uuml;berexpression Krebs Zelle Einmarsch. Weiter und in &Uuml;bereinstimmung mit unseren bisherigen Ermittlungen, beobachteten wir auch, dass eine &Uuml;berexpression von Epsins f&uuml;hrte zu Epithelzellen Migration &uuml;ber die Grenzen der Kolonie. Dar&uuml;ber hinaus zeigen unsere Ergebnisse, dass Epsin-3 ist die Verbesserung der Zellmigration und Invasion der st&auml;rksten Paralog. Interessanterweise ist Epsin-3 Ausdruck nicht weit verbreitet, aber stark eingeschr&auml;nkte wandernden Keratinozyten und aggressive Karzinome. Bei der weiteren Untersuchung haben wir auch Epsin-3 als ausgedr&uuml;ckt als pankreatischen Krebszellen identifiziert. Diese Forschungsergebnisse legen nahe, dass Hochregulation von den EPN3 gen invasive, aggressiven Krebsarten speziell zugeordnet ist. Wir prognostizieren, dass die Untersuchung dieser Links zwischen den endocytic Maschinen und Mechanismen Tumor Verbreitung beteiligt an der Entwicklung neuartiger anti-metastatischen und Anti-Krebs-Strategien beitragen wird.

Epsins Roman Rolle bei Krebs Zelle Invasion.

La familia de adaptadores epsin endoc&#xED;tica se ha encontrado que se upregulated en el c&#xE1;ncer, sin embargo la relevancia de estos hallazgos para esta patolog&#xED;a no es clara. Recientemente hemos demostrado que epsins son necesarios para la migraci&#xF3;n celular. De hecho, la sobreexpresi&#xF3;n epsin promueve la invasi&#xF3;n de las c&#xE9;lulas cancerosas. Por otra parte, y de acuerdo con nuestros resultados anteriores, tambi&#xE9;n se observ&#xF3; que la sobreexpresi&#xF3;n de epsins llevaron a la migraci&#xF3;n de c&#xE9;lulas epiteliales all&#xE1; de las fronteras coloniales. Adem&#xE1;s, nuestros resultados muestran que epsin-3 es la migraci&#xF3;n de c&#xE9;lulas paralog m&#xE1;s potente mejora y la invasi&#xF3;n. Curiosamente, epsin-3 de expresi&#xF3;n no es generalizada, pero muy restringido a los queratinocitos migratorios y los carcinomas agresivos. Tras realizar investigaciones adicionales, que tambi&#xE9;n identific&#xF3; epsin-3, como se expresa en las c&#xE9;lulas de c&#xE1;ncer de p&#xE1;ncreas. Estos hallazgos sugieren que la regulaci&#xF3;n positiva del gen EPN3 est&#xE1; espec&#xED;ficamente asociada con c&#xE1;nceres invasivos y agresivos. Nuestra predicci&#xF3;n es que la investigaci&#xF3;n de estos v&#xED;nculos entre la maquinaria endoc&#xED;tica y los mecanismos implicados en la diseminaci&#xF3;n del tumor va a contribuir al desarrollo de nuevas estrategias de lucha contra la met&#xE1;stasis y la lucha contra el c&#xE1;ncer.

Nuevo papel Epsins &#x26;#39;en la invasi&#xF3;n de c&#xE9;lulas cancer&#xED;genas

Early embryogenesis involves cell fate decisions that define the body axes and establish pools of progenitor cells. Development does not stop once lineages are specified; cells continue to undergo specific maturation events, and changes in gene expression patterns lead to their unique physiological functions. Secretory pancreatic acinar cells mature postnatally to synthesize large amounts of protein, polarize, and communicate with other cells. The transcription factor MIST1 is expressed by only secretory cells and regulates maturation events. MIST1-deficient acinar cells in mice do not establish apical-basal polarity, properly position zymogen granules, or communicate with adjacent cells, disrupting pancreatic function. We investigated whether MIST1 directly induces and maintains the mature phenotype of acinar cells.

Induced Mist1 expression promotes remodeling of mouse pancreatic acinar cells.

Atherosclerotic-associated diseases are the leading cause of death in the United States. Despite recent progress, interventional treatments for atherosclerosis can be complicated by restenosis resulting from neo-intimal hyperplasia. We have previously demonstrated that TGF-β and its downstream signaling protein Smad3 ∶ 1) are up-regulated following vascular injury, 2) together drive smooth muscle cell (SMC) proliferation and migration and 3) enhance the development of intimal hyperplasia. In order to determine a mechanism through which TGF-β/Smad3 promote these effects, Affymetrix gene expression arrays were performed on primary rat SMCs infected with Smad3 and stimulated with TGF-β or infected with GFP alone. More than 200 genes were differentially expressed (>2.0 fold change, p<0.05) in TGF-β/Smad3 stimulated SMCs. We then performed GO term enrichment analysis using the DAVID bioinformatics database and found that TGF-β/Smad3 activated the expression of multiple genes related to either development or cell differentiation, several of which have been shown to be associated with multipotent stem or progenitor cells. Quantitative real-time PCR confirmed up-regulation of several developmental genes including FGF1, NGF, and Wnt11 (by 2.5, 6 and 7 fold, respectively) as well as stem/progenitor cell associated genes CD34 and CXCR4 (by 10 and 45 fold, respectively). In addition, up-regulation of these factors at protein levels were also confirmed by Western blotting, or by immunocytochemistry (performed for CXCR4 and NGF). Finally, TGF-β/Smad3 down regulated transcription of SMC contractile genes as well as protein production of smooth muscle alpha actin, calponin, and smooth muscle myosin heavy chain. These combined results suggest that TGF-β/Smad3 stimulation drives SMCs to a phenotypically altered state of de-differentiation through the up-regulation of developmental related genes.

TGF-β/Smad3 stimulates stem cell/developmental gene expression and vascular smooth muscle cell de-differentiation.

Three major processes, constrictive vessel remodeling, intimal hyperplasia (IH), and retarded re-endothelialization, contribute to restenosis after vascular reconstructions. Clinically used drugs inhibit IH but delay re-endothelialization and also cause constrictive remodeling. Here we have examined halofuginone, an herbal derivative, for its beneficial effects on vessel remodeling and differential inhibition of IH versus re-endothelialization.

Article	Year
MIST1 regulates the pancreatic acinar cell expression of Atp2c2, the gene encoding secretory pathway calcium ATPase 2. Experimental cell research\| PubMed ID: 20599950	2010
Epsins' novel role in cancer cell invasion. Communicative & integrative biology\| PubMed ID: 21509192	2011
Induced Mist1 expression promotes remodeling of mouse pancreatic acinar cells. Gastroenterology\| PubMed ID: 22510200	2012
TGF-β/Smad3 stimulates stem cell/developmental gene expression and vascular smooth muscle cell de-differentiation. PloS one\| PubMed ID: 24718260	2014
Halofuginone stimulates adaptive remodeling and preserves re-endothelialization in balloon-injured rat carotid arteries. Circulation. Cardiovascular interventions\| PubMed ID: 25074254	2014

Daniel DiRenzo

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