Hyperglycemia activates the renin-angiotensin system and induces epithelial-mesenchymal transition in streptozotocin-induced diabetic kidneys

• Published in: Journal of the renin-angiotensin-aldosterone system 2018-07, Vol.19 (3), p.1470320318803009-1470320318803009
• Main Authors: Chen, Chung-Ming, Juan, Shu-Hui, Chou, Hsiu-Chu
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Blood Glucose - metabolism; Body Weight; Cadherins - metabolism; Connective Tissue Growth Factor - metabolism; Diabetes; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - pathology; Epithelial-Mesenchymal Transition; Extracellular Matrix - metabolism; Fibrosis; Gerbillinae; Growth factors; Hyperglycemia; Hyperglycemia - pathology; Inflammation - pathology; Kidney - pathology; Kidneys; Male; Original; Oxidative Stress; Renin-Angiotensin System; Streptozocin; Transforming Growth Factor beta - metabolism
• ISSN: 1470-3203; 1752-8976
• DOI: 10.1177/1470320318803009

Introduction: The renin–angiotensin system and epithelial–mesenchymal transition play crucial roles in the development of kidney fibrosis. The connection between the renin–angiotensin system and transforming growth factor-β in epithelial–mesenchymal transition remains largely unknown. Materials and methods: We assessed oxidative stress, cytokine levels, renal morphology, profibrotic growth factor and renin–angiotensin system component expression, and cell-specific E- and N-cadherin expression in the kidneys of gerbils with streptozotocin-induced diabetes mellitus. Results: Animals in the experimental group received an intraperitoneal injection of streptozotocin to induce diabetes. The diabetic gerbil kidneys presented kidney injury, which was manifested as distorted glomeruli, necrosis of tubular cells, dilated tubular lumen, and brush border loss. Additionally, the diabetic gerbil kidneys exhibited significantly higher expressions of 8-hydroxy-2′-deoxyguanosine, nuclear factor-kB, toll-like receptor 4, tumor necrosis factor-α, transforming growth factor-β, connective tissue growth factor, α-smooth muscle actin, and N-cadherin and higher collagen deposition than did the control gerbil kidneys. Compared with the control kidneys, the diabetic gerbil kidneys exhibited significantly lower E-cadherin expression. These epithelial–mesenchymal transition characteristics were associated with an increase in renin–angiotensin system expression in the diabetic gerbils. Conclusions: We demonstrate that hyperglycemia activated the renin–angiotensin system, induced epithelial–mesenchymal transition, and contributed to kidney fibrosis in an experimental diabetes mellitus model.