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

Abstract

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-β₁ 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.

Keywords:

• ATRA
• glomerulosclerosis
• proteinuria
• TRPC6

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the Natural Science Foundation of China [Nos. 81360115, 81560119, and 81400719], the research subject of Guangxi health department (the high level innovation teams and distinguished Scholars Program of Guangxi Institution of Higher Education) [No. 2014091], and the Scientific Research Projects of Guangxi Institution of Higher Education [No. KY2015YB054].