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

IF 2.5 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Archives of Physiology and Biochemistry 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

{"title":"Cyproheptadine, a SET7/9 inhibitor, reduces hyperglycaemia-induced ER stress alleviating inflammation and fibrosis in renal tubular epithelial cells.","authors":"Himanshu Sankrityayan, Ajinath Kale, Vishwadeep Shelke, Anil Bhanudas Gaikwad","doi":"10.1080/13813455.2022.2105365","DOIUrl":null,"url":null,"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.","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Physiology and Biochemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13813455.2022.2105365","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/8/1 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

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.

查看原文本刊更多论文

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。

求助全文

约1分钟内获得全文求助全文

来源期刊

Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY

CiteScore

6.90

自引率

3.30%

发文量

期刊介绍： Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.