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.
Highlights
Proteinuria is a common clinical manifestation of kidney dysfunction, and is a risk factor for the progression of chronic kidney disease [1]
Our preliminary results suggest that All-trans retinoic acid (ATRA) has a preventive and therapeutic effect on glomerulosclerosis rats induced by adriamycin [7]
Our results showed that on the 12th week after injection, serious proteinuria, increased BUN, and serum creatinine (Scr) were evident in adriamycin-induced rats
Summary
Proteinuria is a common clinical manifestation of kidney dysfunction, and is a risk factor for the progression of chronic kidney disease [1]. Glomerular filtration barrier, including endothelial cells, basement membrane, and podocytes, play an important role in the development of proteinuria [2]. The role of podocytes in glomerular proteinuria has received more and more attention. Numerous studies show that podocyte injury is a key factor in the development of proteinuria and podocyte slit diaphragm (SD) plays a pivotal role in maintaining the integrity of the glomerular filtration barrier [3,4]. TRPC6 is a recently discovered nonselective cation channel, mainly positioned at SD in podocyte [5]. It has been confirmed that TRPC6 interacts with SD structural proteins nephrin and podocin, implying an interaction between the podocyte structural molecules and the ion channels, and regulating structural molecules may help explicate the molecular mechanism of glomerular proteinuria pathogenesis [6]. The mechanisms underlying the antiproteinuria effects of ATRA have not been well illuminated
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