1,25(OH)D 通过上调 DSS 诱导的结肠炎中的 HMGCS2 缓解氧化应激和炎症。

1,25(OH)D alleviates oxidative stress and inflammation through up-regulating HMGCS2 in DSS-induced colitis.

机构信息

Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, China; Key Laboratory of Digestive Diseases of Anhui Province, Hefei, China.

Department of Gastroenterology, Second Affiliated Hospital of Anhui Medical University, Hefei, China.

出版信息

Int Immunopharmacol. 2023 Dec;125(Pt A):111131. doi: 10.1016/j.intimp.2023.111131. Epub 2023 Oct 27.

DOI:10.1016/j.intimp.2023.111131

PMID:38149572

Abstract

BACKGROUND

Previous study found that supplements with active vitamin D3 alleviated experimental colitis. The objective of this study was to investigate the possible role of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a ketone synthase, on vitamin D3 protecting against experimental colitis.

METHODS

HMGCS2 and vitamin D receptor (VDR) were measured in UC patients. The effects of vitamin D deficiency (VDD) and exogenous 1,25(OH)D supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)-treated mice. DSS-induced oxidative stress and inflammation were analyzed in HT-29 cells. HMGCS2 was detected in 1,25(OH)D-pretreated HT-29 cells and mouse intestines. HMGCS2 was silenced to investigate the role of HMGCS2 in 1,25(OH)D protecting against experimental colitis.

RESULTS

Intestinal HMGCS2 downregulation was positively correlated with VDR reduction in UC patients. The in vivo experiments showed that VDD exacerbated DSS-induced colitis. By contrast, 1,25(OH)D supplementation ameliorated DSS-induced colon damage, oxidative stress and inflammation. HMGCS2 was up-regulated after 1,25(OH)D supplementation both in vivo and in vitro. Transfection with HMGCS2-siRNA inhibited antioxidant and anti-inflammatory effects of 1,25(OH)D in DSS-treated HT-29 cells.

CONCLUSION

1,25(OH)D supplementation up-regulates HMGCS2, which is responsible for 1,25(OH)D-mediated protection against oxidative stress and inflammation in DSS-induced colitis. These findings provide a potential therapeutic strategy for alleviating colitis-associated oxidative stress and inflammation.

摘要

背景

先前的研究发现，活性维生素 D3 补充剂可缓解实验性结肠炎。本研究旨在探讨酮合酶 3-羟基-3-甲基戊二酰基辅酶 A 合酶 2（HMGCS2）在维生素 D3 预防实验性结肠炎中的可能作用。

方法

检测 UC 患者中 HMGCS2 和维生素 D 受体（VDR）的表达。在葡聚糖硫酸钠（DSS）处理的小鼠中研究维生素 D 缺乏（VDD）和外源性 1,25（OH）D 补充对实验性结肠炎的影响。在 HT-29 细胞中分析 DSS 诱导的氧化应激和炎症。检测 1,25（OH）D 预处理的 HT-29 细胞和小鼠肠道中的 HMGCS2。沉默 HMGCS2 以研究 HMGCS2 在 1,25（OH）D 预防实验性结肠炎中的作用。

结果

UC 患者肠道 HMGCS2 下调与 VDR 减少呈正相关。体内实验表明，VDD 加重了 DSS 诱导的结肠炎。相比之下，1,25（OH）D 补充改善了 DSS 诱导的结肠损伤、氧化应激和炎症。1,25（OH）D 补充后，体内和体外均上调 HMGCS2。HMGCS2-siRNA 转染抑制了 1,25（OH）D 在 DSS 处理的 HT-29 细胞中的抗氧化和抗炎作用。