TRIM13 Reduces Damage to Alveolar Epithelial Cells in COPD by Inhibiting Endoplasmic Reticulum Stress-Induced ER-Phagy.

IF 4.6 2区医学 Q1 RESPIRATORY SYSTEM

Lung Pub Date : 2024-12-01 Epub Date: 2024-10-09 DOI:10.1007/s00408-024-00753-8

Yaling Xiang, Chuntao Li, Zhiyuan Wang, Jiagang Feng, Jiaqiang Zhang, Yue Yang, Jinbiao Zhou, Jianqing Zhang

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Abstract

Purpose: Tripartite motif-containing protein 13 (TRIM13) directly or indirectly participates in autophagy and apoptosis. However, it remains unclear whether TRIM13 participates in chronic obstructive pulmonary disease (COPD) progression. This study aimed to reveal the molecular mechanisms through which TRIM13 regulates alveolar epithelial cell injury in COPD to provide new molecular targets for COPD treatment.

Methods: The TRIM13 expression levels were determined in clinical COPD patients and a rat emphysema model. A cigarette smoke-induced model of endoplasmic reticulum stress (ERS) and endoplasmic reticulum autophagy (ER-phagy) was developed using A549 cells, and the effects of TRIM13 gene overexpression/knockdown on ERS, ER-phagy, and cell apoptosis were assessed in these cells.

Results: TRIM13 expression was significantly decreased in the lung tissues of COPD patients and rats with emphysema. Moreover, the apoptosis level was significantly increased in the lung tissues of rats with emphysema. TRIM13 gene overexpression reduced the expression levels of ERS-related molecules (GRP78, GRP94, XBP-1, and eIF2a) in the COPD model; it also lowered the ER-phagy level, as evidenced by decreased number of autolysosomes observed by transmission electron microscopy, improved endoplasmic reticulum structure, reduced LC3-II/LC3-I and Beclin1 expression levels, and increased expression level of the autophagy inhibitory molecule Bcl-2. TRIM13 gene knockdown, however, led to opposite results.

Conclusion: TRIM13 expression attenuated alveolar epithelial cell injury in COPD by inhibiting ERS-induced ER-phagy.

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TRIM13 通过抑制内质网应激诱导的内质网吞噬作用减少慢性阻塞性肺疾病对肺泡上皮细胞的损伤

目的：含三方基序蛋白 13（TRIM13）直接或间接参与自噬和细胞凋亡。然而，TRIM13是否参与慢性阻塞性肺病（COPD）的进展仍不清楚。本研究旨在揭示TRIM13调控慢性阻塞性肺疾病肺泡上皮细胞损伤的分子机制，为慢性阻塞性肺疾病的治疗提供新的分子靶点：方法：测定TRIM13在临床COPD患者和大鼠肺气肿模型中的表达水平。方法：在临床 COPD 患者和大鼠肺气肿模型中检测 TRIM13 的表达水平，使用 A549 细胞建立香烟烟雾诱导的内质网应激（ERS）和内质网自噬（ER-phagy）模型，评估 TRIM13 基因过表达/敲除对 ERS、ER-phagy 和细胞凋亡的影响：结果：在慢性阻塞性肺病患者和肺气肿大鼠的肺组织中，TRIM13的表达明显下降。此外，肺气肿大鼠肺组织中细胞凋亡水平明显升高。在慢性阻塞性肺病模型中，TRIM13 基因的过表达降低了 ERS 相关分子（GRP78、GRP94、XBP-1 和 eIF2a）的表达水平；它还降低了 ER 吞噬水平，表现为透射电子显微镜观察到的自溶酶体数量减少，内质网结构改善，LC3-II/LC3-I 和 Beclin1 表达水平降低，自噬抑制分子 Bcl-2 表达水平升高。然而，TRIM13基因敲除却导致了相反的结果：结论：TRIM13的表达可抑制ERS诱导的ER吞噬，从而减轻慢性阻塞性肺疾病肺泡上皮细胞的损伤。

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

Lung 医学-呼吸系统

CiteScore

9.10

自引率

10.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Lung publishes original articles, reviews and editorials on all aspects of the healthy and diseased lungs, of the airways, and of breathing. Epidemiological, clinical, pathophysiological, biochemical, and pharmacological studies fall within the scope of the journal. Case reports, short communications and technical notes can be accepted if they are of particular interest.