Macrophage-to-Myofibroblast Transdifferentiation Contributes to Pulmonary Fibrosis via the MERTK-SPP1-SRC-TKS5 Signaling Axis.

Yungeng Wei, Hua Guo, Xiangsheng Yang, Xiao Xiao Tang

Abstract read

In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in

1citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

Trained Immunity Attenuates Bleomycin-Induced Pulmonary Fibrosis by Promoting AMPK-Mediated Autophagy in Alveolar Macrophages.Biology · 2026
Article

4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Yungeng WeiState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.ORCID https://orcid.org/0009-0009-2418-9761

Hua GuoState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Xiangsheng YangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Xiao Xiao TangState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.ORCID https://orcid.org/0000-0002-3383-0989

Funding

Guangzhou Institute of Respiratory Health Open ProjectNational Natural Science Foundation of China 82270077National Natural Science Foundation of China 82470065National Science and Technology Major Project for Innovative Drug Development SQ2026AAA161178Project supported by Guangzhou National Laboratory and State Key Laboratory of Respiratory Disease GZNL2025B01005R&D Program of Guangzhou National Laboratory GZNL2025A02002

6 · The paper itself

Abstract

In recent years, macrophage-to-myofibroblast transdifferentiation (MMT) has been found in fibrosis-related diseases. We confirmed the presence of MMT in human idiopathic pulmonary fibrosis (IPF) lungs and bleomycin-induced murine model using immunological and molecular methods. Mechanistically, ligand (GAS6)-mediated activation of MERTK on macrophages initiates a sequential signaling cascade involving SPP1, SRC, and TKS5, which collectively drives the transdifferentiation program. Conversely, knockout of MERTK specifically in macrophages or adeno-associated virus (AAV)-mediated knockdown of TKS5 effectively disrupted this MERTK-SPP1-SRC-TKS5 axis, potently suppressing MMT in vitro and in vivo. These interventions significantly attenuated the progression of pulmonary fibrosis, as evidenced by comprehensive assessments including microCT, pulmonary function test, and histopathological analysis. Our findings establish MMT as a key pathogenic mechanism and identify the MERTK-initiated signaling axis as a novel therapeutic target.

Indexed as

Cell Transdifferentiationc-Mer Tyrosine KinaseMacrophagesMyofibroblastsPulmonary FibrosisAnimalsDisease Models, AnimalHumansMiceMice, Inbred C57BLSignal Transductionsrc-Family Kinasesc-Mer Tyrosine Kinasesrc-Family Kinasesidiopathic pulmonary fibrosismacrophagemacrophage‐to‐myofibroblast transdifferentiation (MMT)MERTKTKS5

Identifiers

PMID42133197

DOI10.1002/advs.75620

PMCPMC13336014

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.