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Direct Drug Delivery to Kidney via the Renal Artery

There is a need for directed injections to enable increased and specific renal exposure for efficient evaluation of drug targets in the renal research ...

BioPharmaceuticals R&D

Myeloid-derived C/EBP-homologous protein (CHOP), an effector of the endoplasmic reticulum stress-induced unfolded protein response, promotes macrophage apoptosis in advanced atherosclerosis, but the role of CHOP in vascular smooth muscle cells (VSMCs) in atherosclerosis is not known.

C/EBP-Homologous Protein (CHOP) in Vascular Smooth Muscle Cells Regulates Their Proliferation in Aortic Explants and Atherosclerotic Lesions.

Many long noncoding RNAs (lncRNAs) are enriched in pancreatic islets and several lncRNAs are linked to type 2 diabetes (T2D). While they have emerged as potential players in β-cell biology and T2D, little is known about their functions and mechanisms in human β-cells. We identified an islet-enriched lncRNA, TUNAR (TCL1 upstream neural differentiation-associated RNA), which was upregulated in β-cells of T2D patients and promoted human β-cell proliferation via fine-tuning of the Wnt pathway. TUNAR was upregulated following Wnt agonism by a Glycogen Synthase Kinase-3 (GSK3) inhibitor in human β-cells. Reciprocally, TUNAR repressed a Wnt antagonist Dickkopf-related protein 3 (DKK3) and stimulated Wnt pathway signaling. DKK3 was aberrantly expressed in β-cells of T2D patients and displayed a synchronized regulatory pattern with TUNAR at the single cell level. Mechanistically, DKK3 expression was suppressed by the repressive histone modifier Enhancer of zeste homolog 2 (EZH2). TUNAR interacted with EZH2 in β-cells and facilitated EZH2-mediated suppression of DKK3. These findings reveal a novel cell-specific epigenetic mechanism via islet-enriched lncRNA that fine-tunes the Wnt pathway and subsequently human β-cell proliferation.

Article	Year
C/EBP-Homologous Protein (CHOP) in Vascular Smooth Muscle Cells Regulates Their Proliferation in Aortic Explants and Atherosclerotic Lesions. Circulation research\| PubMed ID: 25872946	2015
The long noncoding RNA TUNAR modulates Wnt signaling and regulates human β-cell proliferation. American journal of physiology. Endocrinology and metabolism\| PubMed ID: 33682459	2021

Alex-Xianghua Zhou

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