title: TRB3 mediates renal tubular cell apoptosis associated with proteinuria.
abstract: Proteinuria may contribute to progressive renal damage by inducing tubulointerstitial inflammation, fibrosis and tubular cell apoptosis, but the underlying mechanisms remain largely unknown. TRB3 is a kinase-like molecule that can modify cellular survival and interfere with signal transduction pathways. We seek to determine the role of TRB3 in renal tubular cell apoptosis associated with proteinuria. Herein, we reported that in a rat tubular cell line, high concentration of albumin augmented TRB3 expression and induced apoptosis, while TRB3 silencing with special small interference RNA significantly attenuated apoptosis. In addition, we found that albumin-induced apoptosis was related to inhibition of Akt phosphorylation, which was, however, partially reversed by TRB3 silencing, indicating that TRB3 worked through Akt pathway in this apoptotic signaling cascade. In vivo, we observed increased TRB3 expression in kidneys of streptozotocin-induced diabetic nephropathy model and albumin-overload nephropathy model, both of which showed overt proteinuria. Notably, proteinuria induced apoptosis in renal tubules, which was less severe after genetically inhibition of TRB3. Taken together, these results suggest that TRB3 mediates renal tubular cell apoptosis induced by protein overload, broadening our understanding of the pathogenesis of progressive proteinuric kidney diseases.
authors.affiliation: Department of Nephrology, Second Hospital of Shandong University, No. 247 Beiyuan Road, Jinan, Shandong Province, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.forename: Aili
authors.initials: A
authors.lastname: Sun
authors.forename: Shasha
authors.initials: S
authors.lastname: Lv
authors.forename: Haiying
authors.initials: H
authors.lastname: Liu
authors.forename: Xiangchun
authors.initials: X
authors.lastname: Liu
authors.forename: Guangju
authors.initials: G
authors.lastname: Guan
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004195:Disease Models, Animal; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011507:Proteinuria / Q000150:complications*; D017208:Rats, Wistar
chemical_list: C502443:Trib3 protein, rat; D017346:Protein Serine-Threonine Kinases