Impaired Alveolar Barrier Integrity Exposes FGFR1 Orchestrating Tight Junction Homeostasis via Occludin Transcription Maintenance.

Jiaqi Zhang, Yang Zhao, Yujie Bao, Bo Yang, Qiaojun He, Zizheng Gao, Bing Xia, Peihua Luo

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Article in International journal of biological sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Jiaqi ZhangCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, P.R. China.

Yang ZhaoCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, P.R. China.

Yujie BaoCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, P.R. China.

Bo YangCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, P.R. China.

Qiaojun HeCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, P.R. China.

Zizheng GaoCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, P.R. China.

Bing XiaDepartment of Thoracic Oncology, Hangzhou Cancer Hospital, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University. Hangzhou 310006, Zhejiang, P.R. China.

Peihua LuoCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, P.R. China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The integrity of the alveolar epithelial barrier is fundamental to pulmonary homeostasis, yet the molecular regulators governing its tight junction (TJ) dynamics remain incompletely understood. Here, we uncover a critical, non-canonical function for FGFR1 as a master regulator of TJ homeostasis. We demonstrate that the RET inhibitor pralsetinib (Pral) induces fatal interstitial lung disease by inhibiting FGFR1, not RET, leading to the selective loss of occludin (OCLN). This disruption stems from transcriptional repression, mediated by the transcription factor CREB1. By integrating

Indexed as

OccludinPulmonary AlveoliReceptor, Fibroblast Growth Factor, Type 1Tight JunctionsAnimalsCyclic AMP Response Element-Binding ProteinHomeostasisMiceMice, KnockoutCyclic AMP Response Element-Binding ProteinFgfr1 protein, mouseOccludinReceptor, Fibroblast Growth Factor, Type 1

Identifiers

PMID42088419

DOI10.7150/ijbs.128209

PMCPMC13137958

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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.