Involvement of PRDX6 in the protective role of MANF in acute lung injury in rats.

IF 1.5 4区医学 Q3 RESPIRATORY SYSTEM

Experimental Lung Research Pub Date : 2025-01-01 Epub Date: 2025-01-24 DOI:10.1080/01902148.2025.2454032

Xiuli Yang, Xueying Xiao, Leiying Zhou, Yujun Shen, Lixia Wang, Qiying Shen

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引用次数: 0

Abstract

Aim/Purpose of the study: Acute lung injury (ALI) is a severe respiratory disease with high mortality, mainly due to overactivated oxidative stress and subsequent pyroptosis. Mesencephalic astrocyte-derived neurotrophic factor (MANF), an inducible secretory endoplasmic reticulum (ER) stress protein, inhibits lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the exact molecular mechanism remains unclear. Peroxiredoxin 6 (PRDX6), a peroxidase with a dual enzymatic function, is essential in regulating oxidative stress, which is closely associated with ALI. Furthermore, PRDX6 is an interacting protein of MANF. Therefore, this study aims to investigate the role of PRDX6 in the protective effect of MANF on ALI.

Materials and Methods: In this study, we used LPS to establish the LPS-induced ALI model. Recombinant human MANF was administrated to wide-type (WT) and PRDX6 knockout (PRDX6^-/-) rats.

Results: In WT rats, MANF reversed the increases of PRDX6, ROS overgeneration, and pyroptosis-related protein-Gasdermin D (GSDMD) induced by LPS challenge. In PRDX6^-/- rats, ROS generation, the protein level of GSDMD-N, and lung injury were not significantly decreased after human recombinant MANF administration in LPS-induced ALI.

Conclusions: PRDX6 is involved in the protective role of MANF on ALI. It is a key target molecule for MANF to exert ALI inhibitory effects.

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PRDX6参与MANF对大鼠急性肺损伤的保护作用。

目的/研究目的：急性肺损伤（Acute lung injury， ALI）是一种死亡率高的严重呼吸系统疾病，主要由过度激活的氧化应激和随后的焦亡引起。中脑星形胶质细胞源性神经营养因子（MANF）是一种诱导分泌性内质网应激蛋白，可抑制脂多糖（LPS）诱导的急性肺损伤（ALI）。然而，确切的分子机制尚不清楚。过氧化氧还蛋白6 （PRDX6）是一种具有双重酶功能的过氧化物酶，在调节氧化应激中起重要作用，与ALI密切相关。此外，PRDX6是MANF的相互作用蛋白。因此，本研究旨在探讨PRDX6在MANF对ALI的保护作用中的作用。材料与方法：本研究采用LPS建立LPS诱导的ALI模型。重组人MANF分别给药于宽型（WT）和PRDX6敲除（PRDX6-/-）大鼠。结果：在WT大鼠中，MANF逆转了LPS刺激引起的PRDX6、ROS过度生成和热腐相关蛋白-气凝胶蛋白D （GSDMD）的增加。在PRDX6-/-大鼠lps诱导的ALI中，给药人重组MANF后，ROS生成、GSDMD-N蛋白水平和肺损伤均未显著降低。结论：PRDX6参与了MANF对ALI的保护作用。它是MANF发挥ALI抑制作用的关键靶分子。

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

Experimental Lung Research 医学-呼吸系统

CiteScore

3.80

自引率

0.00%

发文量

审稿时长

2 months

期刊介绍： Experimental Lung Research publishes original articles in all fields of respiratory tract anatomy, biology, developmental biology, toxicology, and pathology. Emphasis is placed on investigations concerned with molecular, biochemical, and cellular mechanisms of normal function, pathogenesis, and responses to injury. The journal publishes reports on important methodological advances on new experimental modes. Also published are invited reviews on important and timely research advances, as well as proceedings of specialized symposia. Authors can choose to publish gold open access in this journal.