ATRA attenuate proteinuria via downregulation of TRPC6 in glomerulosclerosis rats induced by adriamycin

• Published in: Renal failure 2018-11, Vol.40 (1), p.266-272
• Main Authors: Zhang, Lei, Chen, Xiu-Ping, Qin, He, Jiang, Ling, Qin, Yuan-Han
• Format: Article
• Language: English
• Subjects: Animals; ATRA; Collagen Type IV - metabolism; Creatinine; Disease Models, Animal; Down-Regulation; Doxorubicin - toxicity; Gene expression; glomerulosclerosis; Glomerulosclerosis, Focal Segmental - chemically induced; Glomerulosclerosis, Focal Segmental - drug therapy; Glomerulosclerosis, Focal Segmental - pathology; Glomerulosclerosis, Focal Segmental - urine; Glomerulus; Kidney Glomerulus - metabolism; Kidney Glomerulus - pathology; Kidney Glomerulus - ultrastructure; Laboratory Study; Male; Microscopy, Electron, Transmission; Molecular modelling; mRNA; Protein expression; Proteinuria; Proteinuria - chemically induced; Proteinuria - drug therapy; Proteinuria - pathology; Proteinuria - urine; Rats; Rats, Wistar; RNA, Messenger - metabolism; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Tretinoin - pharmacology; Tretinoin - therapeutic use; TRPC Cation Channels - genetics; TRPC Cation Channels - metabolism; TRPC6; Ultrastructure
• ISSN: 0886-022X; 1525-6049
• DOI: 10.1080/0886022X.2018.1456459

Objective: In this research, we explored the molecular mechanism of proteinuria in glomerulosclerosis rats and the protective effects of ATRA. Methods: This research set up three groups: SHO group, GS group, and ATRA group (15 mg/(kg d), Sigma, St. Louis, MO). The serum creatinine (Scr), urea nitrogen (BUN), and 24-h proteinuria were detected 12 weeks after administration of ATRA. The pathological and ultrastructure changes were observed under light microscope and transmission electron microscope. The protein expression of TGF-β 1 and Col-IV in glomerulus was detected by immunohitochemistry method. The mRNA and the protein expression of glomerular TRPC6 were detected by RT-PCR and Western blot. Results: In the rat model of GS, the expressions of TRPC6 were significantly elevated compared with the normal rat group; however, the use of ATRA down-regulated the expression of TRPC6 in the glomeruli and attenuated glomerulosclerosis and proteinuria. Scr and BUN were also improved by the treatment of ATRA. Conclusions: Our results demonstrated that ATRA could ameliorate glomerulosclerosis and proteinuria in GS, which may be related to suppressed expression of TRPC6.