Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Pilani, India.
Arch Physiol Biochem. 2024 Aug;130(4):411-419. doi: 10.1080/13813455.2022.2105365. Epub 2022 Aug 1.
Persistent hyperglycaemia increases SET7/9 expression and endoplasmic reticulum (ER) stress which causes inflammation, apoptosis, and fibrosis in renal tubular epithelial cells leading to diabetic kidney disease (DKD).
Current study explores the renoprotective potential of a novel SET7/9 inhibitor, Cyproheptadine, and the underlying molecular mechanisms in hyperglycaemia-induced renal tubular epithelial cell injury.
Change in expression of SET7/9, histone H3 lysine (K4) monomethylation (H3K4Me1), inflammatory, fibrotic, and ER stress proteins were evaluated and . NRK-52E cells were used to study the preventive effect of Cyproheptadine against hyperglycaemia-induced ER stress and subsequent inflammation and fibrosis.
SET7/9 and H3K4Me1 expression significantly increased with ER stress, inflammation, apoptosis, and fibrosis, and under hyperglycaemia. However, the cells treated with Cyproheptadine showed significant suppression of H3K4Me1 and reduction in ER stress, inflammation, apoptosis, and fibrosis.
Cyproheptadine prevented hyperglycaemia-induced renal fibrosis and inflammation by reducing H3K4Me1 expression and ER stress.
持续高血糖会增加 SET7/9 的表达和内质网（ER）应激，从而导致肾小管上皮细胞发生炎症、凋亡和纤维化，最终导致糖尿病肾病（DKD）。
本研究旨在探讨新型 SET7/9 抑制剂赛庚啶在高血糖诱导的肾小管上皮细胞损伤中的肾保护作用及其潜在的分子机制。
评估 SET7/9、组蛋白 H3 赖氨酸（K4）单甲基化（H3K4Me1）、炎症、纤维化和 ER 应激蛋白的表达变化。NRK-52E 细胞用于研究赛庚啶对高血糖诱导的 ER 应激及随后的炎症和纤维化的预防作用。
在高血糖条件下，SET7/9 和 H3K4Me1 的表达显著增加，同时伴随着 ER 应激、炎症、凋亡和纤维化的发生。然而，用赛庚啶处理的细胞显示出 H3K4Me1 的显著抑制以及 ER 应激、炎症、凋亡和纤维化的减少。
赛庚啶通过降低 H3K4Me1 表达和 ER 应激，预防了高血糖诱导的肾脏纤维化和炎症。
