Astragaloside IV inhibits excessive mesangial cell proliferation and renal fibrosis caused by diabetic nephropathy via modulation of the TGF‑β1/Smad/miR‑192 signaling pathway

Abstract

Astragaloside IV (ASI) exhibits a wide variety of pharmacological effects in cardiovascular diseases, hepatitis and kidney disease and due to this, ASI has recently become an attractive research target. The present study aimed to determine the effect of ASI on renal fibrosis and the mechanisms underlying its therapeutic effects in diabetic nephropathy (DN). In vitro, ASI was added to rat mesangial cells (RMCs) and cultured with a high level of glucose (HG) to observe the effects exhibited on proliferation and fibrosis-related mRNA and protein expression. In vivo, a DN model was established using streptozotocin administration in rats, and renal injury was evaluated using renal histological examination. The expression levels of related mRNAs and proteins were analyzed using reverse transcription-quantitative PCR, western blot analysis and immunohistochemistry. ASI was demonstrated to downregulate miR-192 expression and inhibit excessive proliferation of RMCs, which was induced by HG, in a dose-dependent manner. Additionally, ASI exhibited a therapeutic effect on DN rats. ASI was also demonstrated to decrease the miR-192 expression and mRNA and protein expression of transforming growth factor-β1 (TGF-β1), Smad3, α-smooth muscle actin (α-SMA) and collagen type 1 (col1), and increase the mRNA and protein expression of Smad7 in vitro and in vivo. These results suggested that ASI exhibited a therapeutic effect on DN, possibly due to the inhibition of excessive mesangial proliferation and renal fibrosis via the TGF-β1/Smad/miR-192 signaling pathway.

Renoprotective effects of Gushen Jiedu capsule on diabetic nephropathy in rats

“…Fortunately, some of the compounds purified from the six herbs of GSJD have been used to treat DN and gained satisfactory results. For instance, astragaloside IV 26,[40][41][42][43][44][45][46] , berberine 39,[47][48][49][50][51] , emodin 38,52 and rhein 53,54 could ameliorate DN by modulating multiple signalling pathways. Therefore, further investigation of the active compounds in GSJD is worthwhile.…”

Noncoding RNAs in Diabetic Nephropathy: Pathogenesis, Biomarkers, and Therapy

“…For instance, miR-370, which is highly increased in the renal DN model, is capable of triggering cell proliferation by targeting canopy 1 (CNPY1) [28]. On the other hand, level of miR-192 is reported to be elevated in high glucose-treated rat MCs, and it regulates MC proliferation and renal fibrosis [59]. Moreover, a recent study showed that miR-379-5p has a critical role in renal fibrosis during DN.…”

The potential role of lncRNAs in diabetes and diabetic microvascular complications

“…The pathogenesis of DN is related to the excessive proliferation and fibrosis of mesangial cells (MCs) [31]. Several lncRNAs have been proved to contribute to regulate MCs proliferation and fibrosis in vivo and in vitro.…”