Cyproheptadine, a SET7/9 inhibitor, reduces hyperglycaemia-induced ER stress alleviating inflammation and fibrosis in renal tubular epithelial cells.

IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-08-01 Epub Date: 2022-08-01 DOI:10.1080/13813455.2022.2105365

Himanshu Sankrityayan, Ajinath Kale, Vishwadeep Shelke, Anil Bhanudas Gaikwad

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引用次数: 0

Abstract

Context: 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).

Objective: 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.

Methods: Change in expression of SET7/9, histone H3 lysine (K4) monomethylation (H3K4Me1), inflammatory, fibrotic, and ER stress proteins were evaluated in-vivo and in-vitro. NRK-52E cells were used to study the preventive effect of Cyproheptadine against hyperglycaemia-induced ER stress and subsequent inflammation and fibrosis.

Results: SET7/9 and H3K4Me1 expression significantly increased with ER stress, inflammation, apoptosis, and fibrosis, in-vivo and in-vitro under hyperglycaemia. However, the cells treated with Cyproheptadine showed significant suppression of H3K4Me1 and reduction in ER stress, inflammation, apoptosis, and fibrosis.

Conclusion: Cyproheptadine prevented hyperglycaemia-induced renal fibrosis and inflammation by reducing H3K4Me1 expression and ER stress.

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SET7/9 抑制剂赛庚啶可降低高血糖诱导的 ER 应激，减轻肾小管上皮细胞的炎症和纤维化。

背景：持续的高血糖会增加 SET7/9 的表达和内质网（ER）应激，从而引起肾小管上皮细胞炎症、凋亡和纤维化，导致糖尿病肾病（DKD）：本研究探讨了新型 SET7/9 抑制剂赛庚啶的肾保护潜力以及高血糖诱导的肾小管上皮细胞损伤的分子机制：方法：评估体内和体外 SET7/9、组蛋白 H3 赖氨酸（K4）单甲基化（H3K4Me1）、炎症蛋白、纤维化蛋白和 ER 应激蛋白的表达变化。用 NRK-52E 细胞研究了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：结果：SET7/9和H3K4Me1的表达随体内和体外高血糖诱导的ER应激、炎症、细胞凋亡和纤维化而显著增加。然而，使用赛庚啶处理的细胞显示出对H3K4Me1的明显抑制，以及ER应激、炎症、细胞凋亡和纤维化的减少：结论：赛普他定通过减少H3K4Me1的表达和ER应激，预防了高血糖诱导的肾纤维化和炎症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464

期刊介绍： ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.