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
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Animals
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Collagen Type IV / metabolism
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Disease Models, Animal
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Down-Regulation
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Doxorubicin / toxicity
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Glomerulosclerosis, Focal Segmental / chemically induced
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Glomerulosclerosis, Focal Segmental / drug therapy*
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Glomerulosclerosis, Focal Segmental / pathology
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Glomerulosclerosis, Focal Segmental / urine
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Kidney Glomerulus / metabolism
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Kidney Glomerulus / pathology
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Kidney Glomerulus / ultrastructure
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Male
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Microscopy, Electron, Transmission
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Proteinuria / chemically induced
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Proteinuria / drug therapy*
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Proteinuria / pathology
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Proteinuria / urine
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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TRPC Cation Channels / genetics
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TRPC Cation Channels / metabolism*
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Transforming Growth Factor beta1 / metabolism
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Tretinoin / pharmacology
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Tretinoin / therapeutic use*
Substances
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Collagen Type IV
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RNA, Messenger
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TRPC Cation Channels
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Transforming Growth Factor beta1
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Trpc6 protein, rat
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Tretinoin
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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].