Samchuleum attenuates diabetic renal injury through the regulation of TGF‑β/Smad signaling in human renal mesangial cells

Abstract

Renal mesangial cell proliferation is a major clinical feature of diabetic nephropathy (DN) and includes glomerulosclerosis and renal fibrosis. Samchuleum (SCE) is a traditional herbal mixture that is recorded in the ancient Korean medical book, Donguibogam. The present study attempted to determine whether SCE treatment was able to improve high glucose (HG)‑induced mesangial cell fibrosis and glomerulosclerosis in primary cultured human mesangial cells. Thymidine incorporation under HG induction was increased, but was decreased by SCE in a dose dependent manner. Pretreatment with SCE led to a downregulation in the expression of cyclins and cyclin‑dependent kinases (CDKs), and an upregulation of the CDK inhibitors, p21waf1/cip1 and p27kip1. In addition, SCE exposure markedly suppressed the reactive oxygen species signaling pathway under HG conditions. HG enhanced the expression levels of fibrosis‑promoting mediators, including collagen IV and connective tissue growth factor, which were markedly attenuated by SCE. SCE treatment inhibited HG‑induced fibronectin mRNA expression and decreased the expression of transforming growth factor (TGF)‑β1, Smad‑2 and Smad‑4, whereas Smad‑7 expression increased under HG. SCE treatment induced the degradation of the extracellular matrix by blocking TGF‑β1/Smad signaling. Therefore, the present study suggested that the inhibitory effect of SCE on mesangial proliferation and renal fibrosis may be an effective therapy in the treatment of renal dysfunction leading to DN.

Evaluation of the inhibitory effect of tacrolimus combined with mycophenolate mofetil on mesangial cell proliferation based on the cell cycle

“…TGF-β1 plays an important role in cell proliferation. After TGF-β1 binds to the serine/threonine kinase receptor on the surface of mesangial cells, the signal is transferred from the cell membrane to the nucleus mediated by Smad proteins (34,35). In the present study, TGF-β1 was used to induce HMc proliferation.…”

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“…Transforming growth factor-β1 (TGF-β1) is an important promoting fibrosis factor, which mediates renal fibrosis and glomerulosclerosis. Continuous hyperglycemia can produce TGF-β1 by stimulating the kidney of DN, which increases the expression and secretion of extracellular matrix protein (ECM) and leads to renal fibrosis (Hills et al, 2018 andYoon et al, 2018). This study showed that the expression of protein TGF-β1 was significantly increased in renal tissue of DN.…”

Ulcer‐healing effects of jumihaidokuto extract in a mouse model of methicillin‐resistant Staphylococcus aureus causing skin infection

“…Although in the case of CB, there have been no reports of specific antibacterial effects, its anti-inflammatory effects associated with inhibition of the iNOS synthesis pathway may contribute to suppressing the cytokine storm induced in response to bacterial invasion. PS and CR extracts also exert an anti-fibrotic effect by suppressing TGF-β expression [29,30]. It has also been suggested that these two constituents may inhibit excessive fibrosis subsequent to ulcerative healing by suppressing the production of TGF-β.…”