MFAP5 aggravates bleomycin‑induced pulmonary fibrosis through activation of the TGF‑β1/Smad signaling pathway

YANG Fan; PENG Meiting; YU Lu; HOU Qinhui; LIU Ying; LIU Yuan; CHENG Zhenshun

doi:10.14188/j.1671-8852.2024.1021

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MFAP5 aggravates bleomycin‑induced pulmonary fibrosis through activation of the TGF‑β1/Smad signaling pathway

更新时间：2026-11-06

- MFAP5 aggravates bleomycin‑induced pulmonary fibrosis through activation of the TGF‑β1/Smad signaling pathway
- Medical Journal of Wuhan University Vol. 46, Issue 12, Pages: 1523-1528(2025)
- 作者机构：
  
  武汉大学中南医院呼吸与危重症医学科湖北武汉 430071
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.1021
  CLC： Q563
- Received：26 December 2024，
  
  Published：25 December 2025
- 稿件说明：
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杨帆,彭梅婷,余露等.MFAP5通过激活TGF‑β1/Smad信号通路加重博来霉素诱导的肺纤维化[J].武汉大学学报（医学版）,2025,46(12):1523-1528.

YANG Fan,PENG Meiting,YU Lu,et al.MFAP5 aggravates bleomycin‑induced pulmonary fibrosis through activation of the TGF‑β1/Smad signaling pathway[J].Medical Journal of Wuhan University,2025,46(12):1523-1528.
杨帆,彭梅婷,余露等.MFAP5通过激活TGF‑β1/Smad信号通路加重博来霉素诱导的肺纤维化[J].武汉大学学报（医学版）,2025,46(12):1523-1528. DOI： 10.14188/j.1671-8852.2024.1021.

YANG Fan,PENG Meiting,YU Lu,et al.MFAP5 aggravates bleomycin‑induced pulmonary fibrosis through activation of the TGF‑β1/Smad signaling pathway[J].Medical Journal of Wuhan University,2025,46(12):1523-1528. DOI： 10.14188/j.1671-8852.2024.1021.

摘要

目的

探讨微纤维相关蛋白5（MFAP5）在博来霉素（BLM）诱导的小鼠肺纤维化中的作用及分子机制。

方法

建立BLM诱导的C57BL/6小鼠肺纤维化模型，使用重组鼠MFAP5蛋白（rmMFAP5）干预并评估其影响。分析MFAP5过表达（MFAP5‑OE）的小鼠肺成纤维细胞，检测纤维化相关分子和TGF‑β1/Smad信号通路的活性。

结果

在体内实验中，rmMFAP5显著加重BLM诱导的小鼠体质量下降及肺纤维化，并增加细胞外基质蛋白的表达。在体外，MFAP5过表达显著上调成纤维细胞中α平滑肌肌动蛋白（α‑SMA）及细胞外基质蛋白的表达，促进成纤维细胞活化和基质合成。机制研究发现，MFAP5通过上调TGF‑β1、Smad2/3及磷酸化Smad2/3水平增强TGF‑β信号活性，抑制TGF‑β通路（SB525334）可显著减少Ⅰ型胶原表达。

结论

MFAP5通过激活TGF‑β1/Smad信号通路，促进肺成纤维细胞活化和基质合成，加重BLM诱导的肺纤维化。

Abstract

Objective

To investigate the role and molecular mechanism of microfibril‑associated protein 5 (MFAP5) in bleomycin (BLM)‑induced pulmonary fibrosis in mice.

Methods

A pulmonary fibrosis model was established in C57BL/6 mice using BLM

and the effects of recombinant MFAP5 protein (rmMFAP5) intervention were evaluated. Primary mouse lung fibroblasts with MFAP5 overexpression (MFAP5‑OE) were analyzed to assess fibrosis‑related molecules and TGF‑β1/Smad signaling activity.

Results

In vivo

rmMFAP5 significantly exacerbated BLM‑induced weight loss and pulmonary fibrosis while increasing extracellular matrix proteins.

In vitro

MFAP5 overexpression markedly upregulated α‑SMA and extracellular matrix proteins

promoting fibroblast activation and matrix synthesis. Mechanistically

MFAP5 enhanced TGF‑β1 signaling by upregulating TGF‑β1

Smad2/3

and phosphorylated Smad2/3 levels. Pharmacological inhibition of TGF‑β1 signaling (SB525334) significantly reduced MFAP5‑induced type I collagen expression.

Conclusion

MFAP5 promotes fibroblast activation and extracellular matrix synthesis via the TGF‑β1/Smad pathway

exacerbating BLM‑induced pulmonary fibrosis.

关键词

Keywords

references

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YANG Fan

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Related Institution

Dept. of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University

Dept. of Respiratory Medicine， Zhongnan Hospital of Wuhan University

武汉大学中南医院呼吸内科

Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University

Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

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