Center of Kidney Dialysis, The Shaanxi Provincial People's Hospital, Xi'an 710068, China.
Dis Markers. 2022 Oct 13;2022:5249910. doi: 10.1155/2022/5249910. eCollection 2022.
We aimed to investigate the role of ganoderic acid A (GAA) in glomerular mesangial cells (GMCs) under high glucose (HG).
GMCs were pretreated with GAA and then cultured under HG condition for 24 h. Cell proliferation was measured by CCK-8 assay. The production of intracellular ROS was determined using DCFH-DA. The activities of SOD and CAT were measured using ELISA kits. The expressions of NOX2, NOX4, fibronectin (FN), collagen IV (col IV), p38, and p-p38 were detected by western blot.
GAA suppressed GMC proliferation in response to HG stimulation. GAA significantly attenuated HG-caused increase in ROS production and decreases in SOD and CAT activities in GMCs. In addition, the increased expressions of NOX2 and NOX4 and NOX activity in HG-induced GMCs were significantly decreased by GAA. Furthermore, GAA greatly inhibited the levels of FN and col IV in HG-stimulated GMCs. Mechanistic investigations showed that HG caused activation of p38 MAPK pathway, whereas the induction was mitigated by GAA. Notably, the specific agonist of p38 MAPK pathway (P79350) reversed the effects of GAA on GMCs.
GAA protected GMCs from HG-induced oxidative stress and ECM production, which was mediated by the inhibition of the p38 MAPK pathway.
研究赤芝酸 A（GAA）在高糖（HG）条件下对肾小球系膜细胞（GMC）的作用。
用 GAA 预处理 GMC，然后在 HG 条件下培养 24 h。用 CCK-8 法测定细胞增殖。用 DCFH-DA 测定细胞内 ROS 的产生。用 ELISA 试剂盒测定 SOD 和 CAT 的活性。用 Western blot 检测 NOX2、NOX4、纤维连接蛋白（FN）、IV 型胶原（col IV）、p38 和 p-p38 的表达。
GAA 抑制 HG 刺激引起的 GMC 增殖。GAA 显著减轻 HG 引起的 GMC 中 ROS 产生增加、SOD 和 CAT 活性降低。此外，GAA 还显著降低了 HG 诱导的 GMC 中 NOX2 和 NOX4 的表达和 NOX 活性。此外，GAA 还显著抑制了 HG 刺激的 GMC 中 FN 和 col IV 的水平。机制研究表明，HG 激活了 p38 MAPK 通路，而 GAA 减轻了这种诱导。值得注意的是，p38 MAPK 通路的特异性激动剂（P79350）逆转了 GAA 对 GMC 的作用。
GAA 保护 GMC 免受 HG 诱导的氧化应激和 ECM 产生，这是通过抑制 p38 MAPK 通路介导的。
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