MAT2A抑制可抑制感染的人牙龈成纤维细胞中的炎症。

MAT2A inhibition suppresses inflammation in -infected human gingival fibroblasts.

作者信息

Jiang Lishan, Li Jingwen, Ji Kun, Lei Lang, Li Houxuan

机构信息

Nanjing Stomatological Hospital, Affiliated Hospital of medical School, Nanjing University, Nanjing, China.

Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of medical School, Nanjing University, Nanjing, China.

出版信息

J Oral Microbiol. 2023 Dec 15;16(1):2292375. doi: 10.1080/20002297.2023.2292375. eCollection 2024.

DOI:10.1080/20002297.2023.2292375

PMID:38130504

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10732205/

Abstract

BACKGROUND

Methionine adenosyl transferase II alpha (MAT2A) is the key enzyme to transform methionine into S-adenosylmethionine (SAM), the main methylgroup donor involved in the methylation. The purpose of our study wasto explore whether MAT2A-mediated methionine metabolism affected theexpression of inflammatory cytokines in human gingival fibroblasts(hGFs).

METHODS

Both healthy and inflamed human gingiva were collected. HGFs werecultured and treated with P. gingivalis, with or without MAT2Ainhibitor (PF9366), small interference RNA (siRNA), or extrinsic SAMpretreatment. The levels of inflammatory cytokines were detected byreal-time PCR, western blotting, and ELISA. SAM levels were detectedby ELISA. The nuclear factor-kappa B (NF-κB) and mitogen-activatedprotein kinase (MAPK) pathway was explored by western blotting.

RESULTS

The expression of MAT2A was increased in the inflamed tissues. P.gingivalis infection promoted the expression of MAT2A and SAM inhGFs. Meanwhile, PF9366 and MAT2A-knockdown significantly decreasedexpression of inflammatory cytokines and SAM production. PF9366inhibited activation of NF-κB/MAPK pathway in P. gingivalis-treatedhGFs.

CONCLUSIONS

MAT2A-mediated methionine metabolism promoted P. gingivalis-inducedinflammation in hGFs. Targeting MAT2A may provide a novel therapeuticmethod for modulating periodontitis.

摘要

背景

蛋氨酸腺苷转移酶IIα（MAT2A）是将蛋氨酸转化为S-腺苷甲硫氨酸（SAM）的关键酶，SAM是参与甲基化的主要甲基供体。本研究的目的是探讨MAT2A介导的蛋氨酸代谢是否影响人牙龈成纤维细胞（hGFs）中炎性细胞因子的表达。

方法

收集健康和发炎的人牙龈组织。培养hGFs并用牙龈卟啉单胞菌处理，同时给予或不给予MAT2A抑制剂（PF9366）、小干扰RNA（siRNA）或外源性SAM预处理。通过实时PCR、蛋白质印迹法和酶联免疫吸附测定（ELISA）检测炎性细胞因子水平。通过ELISA检测SAM水平。通过蛋白质印迹法探究核因子-κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路。