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

Ren Fail. 2018 Nov;40(1):266-272. doi: 10.1080/0886022X.2018.1456459.

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; TRPC6; glomerulosclerosis; proteinuria.

MeSH terms

  • Animals
  • Collagen Type IV / metabolism
  • Disease Models, Animal
  • Down-Regulation
  • Doxorubicin / toxicity
  • Glomerulosclerosis, Focal Segmental / chemically induced
  • Glomerulosclerosis, Focal Segmental / drug therapy*
  • Glomerulosclerosis, Focal Segmental / pathology
  • Glomerulosclerosis, Focal Segmental / urine
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / ultrastructure
  • Male
  • Microscopy, Electron, Transmission
  • Proteinuria / chemically induced
  • Proteinuria / drug therapy*
  • Proteinuria / pathology
  • Proteinuria / urine
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • Transforming Growth Factor beta1 / metabolism
  • Tretinoin / pharmacology
  • Tretinoin / therapeutic use*

Substances

  • Collagen Type IV
  • RNA, Messenger
  • TRPC Cation Channels
  • Transforming Growth Factor beta1
  • Trpc6 protein, rat
  • Tretinoin
  • Doxorubicin

Grants and 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].