title: TRB3, up-regulated in kidneys of rats with type1 diabetes, mediates extracellular matrix accumulation in vivo and in vitro.
abstract: OBJECTIVE
  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.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Ji'nan, Shandong Province, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, The Second Hospital of Shandong University, Ji'nan, Shandong Province, China.
authors.forename: Aili
authors.initials: A
authors.lastname: Sun
authors.affiliation: Department of Nephrology, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Ji'nan, Shandong Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Ji'nan, Shandong Province, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Lv
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Ji'nan, Shandong Province, China.
authors.forename: Xiangchun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Ji'nan, Shandong Province, China. Electronic address: guangj@sdu.edu.cn.
authors.forename: Guangju
authors.initials: G
authors.lastname: Guan
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Ji'nan, Shandong Province, China. Electronic address: gangliu@sdu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C502443:Trib3 protein, rat; D017346:Protein Serine-Threonine Kinases
keywords: Albumin-overload; Diabetic nephropathy; Extracellular matrix accumulation; Proximal tubular cells; TRB3