Effect of Curcumin on High Glucose-Induced Glomerular Mesangial Cell Fibrosis via Modulating the Notch1/Hes1 Pathway
WANG Yarui1, KONG Wenwen2, ZHU Weina3, CHEN Ting1, SUN Long1, XIA Qin1, ZHAO Shan1*
This study aims to investigate the effect of Cur (curcumin) on HG (high glucose)-induced fibrosis in rat glomerular mesangial cells (HBZY-1) via modulating the Notch1/Hes1 pathway. CCK-8 assay was used to screen the appropriate concentration of Cur. HBZY-1 cells were divided into normal control (NG) group, hyperosmotic control (NG+M) group, HG group, Cur low-concentration (HG+Cur-L) group, Cur high-concentration (HG+Cur-H) group, Notch1 inhibitor DAPT (HG+DAPT) group, Notch1 activator Jagged1 (HG+Jagged1) group, and Cur-H+Notch1 activator Jagged1 (HG+Cur-H+Jagged1) group. Cell proliferation was assessed by EdU staining; protein expression was determined by Western blot and immunofluorescence staining; levels of IL-1β (interleukin-1β), TNF-α (tumor necrosis factor-α), IL-6, and MCP-1 (monocyte chemoattractant protein-1) were detected by ELISA; levels of MDA (malondialdehyde), SOD (superoxide dismutase), and GSH-Px (glutathione peroxidase) were measured using assay kits; and mRNA levels of Notch1 and Hes1 were quantified by qRT-PCR. Compared with the NG group, the HG group showed a significant increase in EdU-positive rate (P<0.05); elevated fibrosis-related indicators [protein expression of α-SMA (α-smooth muscle actin), TGF-β1 (transforming growth factor-β1), collagen I, and FN (fibronectin), as well as mean fluorescence intensity of α-SMA and collagen Ⅰ (P<0.05)]; elevated levels of inflammatory or oxidative stress indicators IL-1β, TNF-α, IL-6, MCP-1, and MDA, and decreased levels of SOD and GSH-Px (P<0.05); and upregulated pathway-related molecules [Notch1 and Hes1 mRNA levels, as well as protein expression of Notch1, NICD (Notch intracellular domain), and Hes1 (P<0.05)]. No significant differences were observed between the NG+M and NG groups. Compared with the HG group, the above abnormal indicators were reversed to varying degrees in the HG+Cur-L, HG+Cur-H, and HG+DAPT groups, with the HG+Cur-H group showing more pronounced effects. The Notch1 activator Jagged1 significantly aggravated HG-induced injury and partially reversed the cytoprotective effects of high-concentration curcumin on HBZY-1 cells. Cur may alleviate HG-induced fibrosis in HBZY-1 cells by inhibiting the Notch1/Hes1 pathway, mitigating associated inflammation and oxidative stress.
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