{"doi":"10.1101/2023.04.24.538195","title":"Tension sensing by FAK governs nuclear mechanotransduction, endothelial transcriptome and fate","abstract":"Abstract Vascular endothelium forms a restrictive barrier to defend the underlying tissue against uncontrolled influx of circulating protein and immune cells. Mechanisms that mediate the transition from restrictive to leaky endothelium, a hallmark of tissue injury exemplified by acute lung injury (ALI), remain elusive. Using endothelial cell (EC)-Fak -/- mice, we show that FAK sensing and transmission of mechanical tension to the EC nucleus governs cell fate. In FAK- deleted EC, increased EC tension induced by Rho kinase caused tyrosine phosphorylation of nuclear envelope protein, emerin at Y74/Y95, and its localization in a nuclear cap. Activated emerin stimulated DNMT3a activity and methylation of the KLF2 promoter, impairing the restrictive EC transcriptome, including S1PR1 . Inhibiting emerin phosphorylation or DNMT3a activity enabled KLF2 transcription of S1PR1 , rescuing the restrictive EC phenotype in EC-Fak -/- lungs. Thus, FAK sensing of tension transmission to the nucleus is crucial for maintaining a restrictive EC fate and lung homeostasis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":399142,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1175211,"name":"Pascal Yazbeck","orcid":"0000-0003-4282-5345","position":1,"is_corresponding":false},{"id":312211,"name":"Mohammad Tauseef","orcid":"0000-0001-5317-4379","position":2,"is_corresponding":false},{"id":486240,"name":"Mumtaz Anwar","orcid":"0000-0001-5711-7312","position":3,"is_corresponding":false},{"id":1175212,"name":"Faruk Hossen","orcid":"0000-0002-2864-3046","position":4,"is_corresponding":false},{"id":1175213,"name":"Sayanti Datta","orcid":"0000-0002-6833-1899","position":5,"is_corresponding":false},{"id":562310,"name":"V. Vigneshwaran","orcid":"0000-0003-3695-7384","position":6,"is_corresponding":false},{"id":310862,"name":"Jagdish Chandra Joshi","orcid":"0000-0002-9468-3046","position":7,"is_corresponding":false},{"id":1175440,"name":"Nityanand Srivastava","orcid":null,"position":8,"is_corresponding":false},{"id":417887,"name":"Stephen Lenzini","orcid":"0000-0002-2585-4817","position":9,"is_corresponding":false},{"id":490035,"name":"Guangjin Zhou","orcid":"0000-0001-6309-6386","position":10,"is_corresponding":false},{"id":235277,"name":"James Lee","orcid":"0000-0002-1762-1677","position":11,"is_corresponding":false},{"id":490036,"name":"Mukesh K. Jain","orcid":"0000-0002-1301-292X","position":12,"is_corresponding":false},{"id":344179,"name":"Jae‐Won Shin","orcid":"0000-0003-4823-6373","position":13,"is_corresponding":false},{"id":241668,"name":"Dolly Mehta","orcid":"0000-0003-0945-9304","position":14,"is_corresponding":false},{"id":312209,"name":"Md Zahid Akhter","orcid":"0000-0002-1602-3704","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:51.724387Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}