Evidence map›Paper›PMID 41668071›Full record

ArticleRespiratory research2026

The circadian clock component PER2 deficiency aggravates airway epithelial remodeling through Wnt/β-catenin signaling pathway.

Shuwen Zhang, Jiangtao Lin

Abstract read
In one paragraph

Article in Respiratory research, 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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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

2 authors.

Shuwen ZhangPeking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China.
Jiangtao LinPeking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China. jiangtao_l@263.net.

Funding

National Natural Science Foundation of China 8217010602
6 · The paper itself

Abstract

backgroundEpithelial-mesenchymal transition (EMT) represents a key pathological mechanism underlying airway remodeling in asthma. However, the role of the circadian clock component PER2 in asthma-associated airway remodeling remains unclear.

objectiveThis study aimed to investigate the role of the circadian clock component PER2 in the pathogenesis of EMT in asthma and to elucidate the underlying molecular mechanism.

methodsPER2 expression on airway epithelial and association between of PER2 and lung function were determined using data from public databases. The wild-type (WT) and Per2 knockout (Per2⁻/⁻) mice was induced ovalbumin (OVA) to establish asthma model. Airway hyperresponsiveness (AHR), inflammation, mucus production, fibrosis, and EMT markers were assessed. Human bronchial epithelial cells (BEAS-2B) were stimulated with TGF-β1 to induce EMT, followed by PER2 overexpression. RNA sequencing, Western blot, immunofluorescence, and functional migration assays were employed. The Wnt/β-catenin agonist SKL2001 was used to rescue the phenotype. The role of melatonin was also investigated in vivo.

resultsBioinformatic and clinical data identified PER2 as a key downregulated circadian gene in asthma, correlating with impaired lung function. Per2⁻/⁻ mice exposed to OVA exhibited exacerbated AHR, airway inflammation, mucus hypersecretion, subepithelial fibrosis, and enhanced EMT markers compared to WT mice exposed to OVA. RNA-seq and pathway analysis revealed that PER2 deficiency activated the Wnt/β-catenin pathway. In vitro, TGF-β1 downregulated PER2 expression. Overexpression of PER2 in cells suppressed TGF-β1-induced EMT, migration, and inhibited Wnt/β-catenin signaling activation. The protective effects of PER2 were partly reversed by the β-catenin agonist SKL2001. Finally, melatonin alleviated OVA-induced EMT by upregulating the PER2.

conclusionThis study demonstrates that the circadian clock component PER2 plays a critical protective role in inhibiting airway remodeling in asthma by suppressing EMT through the Wnt/β-catenin signaling pathway. Furthermore, melatonin exerts its therapeutic effects by upregulating PER2. Targeting the PER2 may represent a novel therapeutic strategy for mitigating airway remodeling in asthma.

Indexed as

Airway RemodelingAsthmabeta CateninPeriod Circadian ProteinsWnt Signaling PathwayAnimalsEpithelial-Mesenchymal TransitionHumansMaleMiceMice, Inbred C57BLMice, KnockoutOvalbuminbeta CateninOvalbuminPER2 protein, humanPer2 protein, mousePeriod Circadian ProteinsAirway remodelingAsthmaCircadian clockEpithelial-mesenchymal transitionPER2

Identifiers

PMID41668071
PMCPMC12990575

What Socratic holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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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 Socratic graph.