Weiwei Wang1, Aili Sun2, Wei Lv3, Jing Cheng1, Shasha Lv1, Xiangchun Liu1, Guangju Guan4, Gang Liu5. 1. Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Ji'nan, Shandong Province, China. 2. Department of Endocrinology, The Second Hospital of Shandong University, Ji'nan, Shandong Province, China. 3. Department of Nephrology, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China. 4. Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Ji'nan, Shandong Province, China. Electronic address: guangj@sdu.edu.cn. 5. Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Ji'nan, Shandong Province, China. Electronic address: gangliu@sdu.edu.cn.
Abstract
AIMS: Fibrosis is the final disorder of most chronic kidney disease including diabetic nephropathy (DN), but the mechanisms are not fully understood. The present study aims to determine whether TRB3 participates in fibrogenesis in DN. METHODS: Type1 diabetes was induced in male Wistar rats via intraperitoneal injection of streptozotocin (STZ). The expression of TRB3 and extracellular matrix (ECM) protein collagen I and fibronectin was investigated in kidneys of rats with diabetes and NRK-52E cells (a rat proximal tubular cell line) stimulated with albumin-overload. Rats without diabetes and NRK-52E cells without albumin stimulation served as control. Then gene silencing was used to study whether TRB3 participated in accumulation of collagen I and fibronectin in vivo and in vitro. RESULTS: TRB3 is up-regulated in renal tubules of kidneys of rats with diabetes, especially proximal tubules. Albumin-overload can augments TRB3 expression and increase collagen I and fibronectin secretion in NRK-52E cells. Importantly, silencing of TRB3 alleviates collagen I and fibronectin accumulation in kidneys of rats with diabetes and NRK-52E cells induced by albumin-overload. CONCLUSIONS: TRB3 mediates ECM accumulation in kidneys of rats with STZ-induced type1 diabetes and proximal tubular cells induced by albumin-overload, suggesting a potential target for treatment of DN.
AIMS: Fibrosis is the final disorder of most chronic kidney disease including diabetic nephropathy (DN), but the mechanisms are not fully understood. The present study aims to determine whether TRB3 participates in fibrogenesis in DN. METHODS: Type1 diabetes was induced in male Wistar rats via intraperitoneal injection of streptozotocin (STZ). The expression of TRB3 and extracellular matrix (ECM) protein collagen I and fibronectin was investigated in kidneys of rats with diabetes and NRK-52E cells (a rat proximal tubular cell line) stimulated with albumin-overload. Rats without diabetes and NRK-52E cells without albumin stimulation served as control. Then gene silencing was used to study whether TRB3 participated in accumulation of collagen I and fibronectin in vivo and in vitro. RESULTS:TRB3 is up-regulated in renal tubules of kidneys of rats with diabetes, especially proximal tubules. Albumin-overload can augments TRB3 expression and increase collagen I and fibronectin secretion in NRK-52E cells. Importantly, silencing of TRB3 alleviates collagen I and fibronectin accumulation in kidneys of rats with diabetes and NRK-52E cells induced by albumin-overload. CONCLUSIONS:TRB3 mediates ECM accumulation in kidneys of rats with STZ-induced type1 diabetes and proximal tubular cells induced by albumin-overload, suggesting a potential target for treatment of DN.
Authors: Laura Martinez-Campesino; Klaudia Kocsy; Jaime Cañedo; Jessica M Johnston; Charlotte E Moss; Simon A Johnston; Stephen Hamby; Alison H Goodall; Jessica Redgrave; Sheila E Francis; Endre Kiss-Toth; Heather L Wilson Journal: Front Cardiovasc Med Date: 2022-08-26