Urotensin II Induces ER Stress and EMT and Increase Extracellular Matrix Production in Renal Tubular Epithelial Cell in Early Diabetic Mice
| Autor: | Guan-Jong Chen, Fei Wu, Qiong Bai, Chao-Shu Tang, Xinxin Pang, Ai-Hua Zhang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Urotensin II
0301 basic medicine lcsh:Diseases of the circulatory (Cardiovascular) system medicine.medical_specialty Epithelial-Mesenchymal Transition Urotensins lcsh:RC870-923 Cell Line Diabetes Mellitus Experimental Mice 03 medical and health sciences Type IV collagen chemistry.chemical_compound Downregulation and upregulation Diabetic Nephropathy Internal medicine lcsh:Dermatology medicine Animals Humans Diabetic Nephropathies Epithelial–mesenchymal transition Receptor Endoplasmic Reticulum Chaperone BiP Mice Knockout Kidney biology EMT Epithelial Cells General Medicine lcsh:RL1-803 lcsh:Diseases of the genitourinary system. Urology Extracellular Matrix Mice Inbred C57BL Fibronectin Kidney Tubules 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry lcsh:RC666-701 Nephrology Endoplasmic reticulum stress Unfolded protein response biology.protein Cardiology and Cardiovascular Medicine Urotensin-II |
| Zdroj: | Kidney & Blood Pressure Research, Vol 41, Iss 4, Pp 434-449 (2016) |
| ISSN: | 1423-0143 1420-4096 |
| DOI: | 10.1159/000443445 |
| Popis: | Background/Aims: Urotensin II (UII) and its receptor are highly expressed in the kidney tissue of patients with diabetic nephropathy (DN). The aim of this study is to examine the roles of UII in the induction of endoplasmic reticulum stress (ER stress) and Epithelial-mesenchymal transition (EMT) in DN in vivo and in vitro. Methods: Kidney tissues were collected from patients with DN. C57BL/6 mice and mice with UII receptor knock out were injected with two consecutive doses of streptozotocin to induce diabetes and were sacrificed at 3th week for in vivo study. HK-2 cells in vitro were cultured and treated with UII. Markers of ER stress and EMT, fibronectin and type IV collagen were detected by immunohistochemistry, real time PCR and western blot. Results: We found that the expressions of protein of UII, GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were upregulated while E-cadherin protein was downregulated as shown by immunohistochemistry or western blot analysis in kidney of diabetic mice in comparison to normal control; moreover expressions of GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were inhibited while E-caherin expression was enhanced in kidney in diabetic mice with UII receptor knock out in comparison to C57BL/6 diabetic mice. In HK-2 cells, UII induced upregulation of GRP78, CHOP, ALPHA-SMA, fibroblast-specifc protein 1(FSP-1), fibronectin and type collagen and downregulation of E-cadherin. UII receptor antagonist can block UII-induced ER stress and EMT; moreover, 4-PBA can inhibit the mRNA expression of ALPHA-SMA and FSP1 induced by UII in HK-2 cells. Conclusions: We are the first to verify UII induces ER stress and EMT and increase extracellular matrix production in renal tubular epithelial cell in early diabetic mice. Moreover, UII may induce renal tubular epithelial EMT via triggering ER stress pathway in vitro, which might be the new pathogenic pathway for the development of renal fibrosis in DN. |
| Databáze: | OpenAIRE |
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