ArticleThorax2023
Cigarette smoking is a secondary cause of folliculin loss.
Article in Thorax, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- Hyperactivation of mTORC1 signaling mediates folliculin deficiency-induced pulmonary cyst formation in Birt-Hogg-Dubé syndrome.The Journal of clinical investigation · 2026Article
- A familial case of Birt-Hogg-Dubé syndrome complicated with lung cancer: a case report and literature review.Frontiers in medicine · 2025Article
- A case report of Birt-Hogg-Dubé syndrome associated with severe airway obstruction in a 62-year-old female smoker.Respirology case reports · 2024Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBirt-Hogg-Dubé syndrome (BHD) is a clinical syndrome manifesting with cystic lung disease and pneumothorax. Features of BHD result from the loss-of-function mutations of the folliculin (
objectiveGiven that COPD often shares structural features with BHD, we investigated the link between COPD, cigarette smoke (CS) exposure and FLCN expression.
methodsWe measured the expression of FLCN in human COPD lungs and CS-exposed mouse lungs, as well as in CS extract (CSE)-exposed immortalised human airway epithelial cells by immunoblotting.
resultsWe found that the lung FLCN protein levels in smokers with COPD and CS exposure mice exhibit a marked decrease compared with smokers without COPD and room air exposure mice, respectively. We confirmed CS induced degradation of FLCN in immortalised human bronchial epithelial Beas-2B cells via ubiquitin proteasome system. Further, siRNA targeting FLCN enhanced CSE-induced cytotoxicity. By contrast, FLCN overexpression protected cells from CSE-induced cytotoxicity. We found that FBXO23, the ubiquitin E3 ligase subunit, specifically binds to and targets FLCN for degradation. Inhibition of ATM (ataxia-telangiectasia mutated) attenuated CSE induced FLCN degradation, suggesting a role of ATM in FLCN proteolysis. We further confirmed that the mutant of major FLCN phosphorylation site serine 62A is resistant to CSE-induced degradation and cytotoxicity.
conclusionsOur study demonstrates that CS exposure is a secondary cause of FLCN deficiency due to the enhanced proteolysis, which promoted airway epithelial cell death.
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Registered trials
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.