Combination therapy with DHA and BMSCs suppressed podocyte injury and attenuated renal fibrosis by modulating the TGF- β 1/Smad pathway in MN mice

Abstract

Artemisinin has immunomodulatory, anti-inflammatory, and antifibrotic effects. Some studies have demonstrated that artemisinins have a protective effect on the kidney. DHA is a derivative of artemisinin and has effects similar to those of artemisinin. Human bone marrow-derived mesenchymal stem cells (BMSCs) accelerate renal repair following acute injury. In the study, we investigated the effects of combination therapy with DHA and BMSCs on membranous nephropathy (MN) mice. The 24-h urinary protein, serum total cholesterol (TC) and triglyceride (TG) levels, and renal histopathology, were measured to evaluate kidney damage. Anti-PLA2R, IgG, and complement 3 (C3) were detected by ELISA. The expression levels of the podocyte injury-related proteins were analyzed by immunohistochemistry. The protein expression levels of α -SMA, ED-1, TGF- β 1, p-Smad2, and p-Smad3 were detected by western blot to analyze renal fibrosis and its regulatory mechanism. Results showed that combination therapy with DHA and BMSCs significantly ameliorated kidney damage in MN model mice by decreasing the levels of 24 h urinary protein, TC and TG. This combination therapy also improved renal histology and reduced the expression of IgG and C3 in the glomerulus. In addition, this combination therapy decreased the expression of podocin and nephrin and relieved renal fibrosis by downregulating α -SMA and ED-1. Furthermore, this combination therapy suppressed TGF- β 1 expression and Smad2/3 phosphorylation. This result (i.e., this combination therapy inhibited the TGF- β 1/Smad pathway) was also supported in vitro . Taken together, combination therapy with DHA and BMSCs ameliorated podocyte injury and renal fibrosis in MN mice by downregulating the TGF β 1/Smad pathway.

Ameliorative effects of glycine on cobalt chloride‐induced hepato‐renal toxicity in rats

“…Therefore, the observed decrease in the expression of podocin in renal tissues of rats treated with glycine in this study suggests a preservation of the structural integrity of renal tissues and therefore indicates that glycine is a potent renoprotective agent against renal toxicities associated with CoCl 2 exposures. Recent experimental studies also confirmed high expression of podocin as a novel biomarker of renal damage during acute kidney injury [49][50][51]. In conclusion, the results of this study clearly demonstrate the protective effects of glycine against tissue injuries and derangement of normal physiological functioning of the hepatic and renal systems in rats.…”

“…Therefore, the observed decrease in the expression of podocin in renal tissues of rats treated with glycine in this study suggests a preservation of the structural integrity of renal tissues and therefore indicates that glycine is a potent renoprotective agent against renal toxicities associated with CoCl 2 exposures. Recent experimental studies also confirmed high expression of podocin as a novel biomarker of renal damage during acute kidney injury 49–51 …”

“…Recent experimental studies also confirmed high expression of podocin as a novel biomarker of renal damage during acute kidney injury. 49 , 50 , 51 …”