{"doi":"10.26508/lsa.202503460","title":"Brain vascular stability relies on PAK2–cilia–PDGF-BB–HSPGs on basolateral side of endothelium","abstract":"Endothelial cells (ECs) in the brain communicate with mural cells to facilitate vascular stability. Platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor receptor-β (PDGFR-β) signaling mechanism at EC-mural cell interface helps stabilize the vasculature. How this paracrine signaling is mediated is not known. Our laboratory studies endothelial cilia, a microtubule-based organelle, and its role in promoting vascular stability. We discovered that brain endothelial cilia are located primarily on the basolateral side, and PDGF-BB is expressed in EC cilium. Thus, we hypothesized that endothelium cilium in conjunction with PDGF-BB on the basolateral side is responsible for mural cell recruitment. In this study, using a combination of zebrafish, mice, and human brain model systems, we have established a signaling paradigm wherein p21-activated kinase (PAK2) and ADP-ribosylation factor-13b (ARL13b) in ECs induce secretion of PDGF-BB. PDGF-BB associates with heparan sulfate proteoglycans (HSPGs) to form a gradient around ECs. Disrupting PAK2 affects ciliogenesis, HSPGs, and PDGF-BB gradient. We unravel a new mechanism involving endothelial cilia/PAK2-mediated PDGF-BB secretion, and retention by periendothelial HSPGs to promote vascular stability via recruiting mural cells.","journal":"Life Science Alliance","year":2025,"id":529672,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1409497,"name":"K. Thirugnanam","orcid":null,"position":1,"is_corresponding":false},{"id":1409498,"name":"Xuehong. Song","orcid":null,"position":2,"is_corresponding":false},{"id":350,"name":"Hua Yang","orcid":"0000-0002-4876-4072","position":3,"is_corresponding":false},{"id":669764,"name":"Mariella Errede","orcid":"0000-0002-8163-2338","position":4,"is_corresponding":false},{"id":1114756,"name":"Francesco Girolamo","orcid":"0000-0001-8706-3386","position":5,"is_corresponding":false},{"id":1409011,"name":"Thomas Neumann","orcid":"0000-0002-9443-4648","position":6,"is_corresponding":false},{"id":1409499,"name":"Andrea MARZULLO","orcid":null,"position":7,"is_corresponding":false},{"id":1409500,"name":"Sepand Bafti","orcid":null,"position":8,"is_corresponding":false},{"id":1409501,"name":"Kayla Vanderhoef","orcid":null,"position":9,"is_corresponding":false},{"id":918817,"name":"Kevin R. Rarick","orcid":"0000-0003-3356-3769","position":10,"is_corresponding":false},{"id":444934,"name":"Andrew D. Spearman","orcid":"0000-0003-2035-5258","position":11,"is_corresponding":false},{"id":444935,"name":"Amy Pan","orcid":"0000-0002-7199-7704","position":12,"is_corresponding":false},{"id":1409502,"name":"Claudia Álvarez Álvarez","orcid":null,"position":13,"is_corresponding":false},{"id":1140605,"name":"J. H. Yang","orcid":"0000-0002-9285-098X","position":14,"is_corresponding":false},{"id":189964,"name":"Fuming Zhang","orcid":null,"position":15,"is_corresponding":false},{"id":1409503,"name":"Jonathan Dordick","orcid":null,"position":16,"is_corresponding":false},{"id":1114757,"name":"Daniela Virgintino","orcid":"0000-0003-1041-5341","position":17,"is_corresponding":false},{"id":49239,"name":"L. Wang","orcid":"0009-0007-8928-0326","position":18,"is_corresponding":false},{"id":316614,"name":"Ramani Ramchandran","orcid":"0000-0002-3555-6119","position":19,"is_corresponding":false},{"id":316608,"name":"Shubhangi Prabhudesai","orcid":"0000-0002-2300-0316","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:51:01.235017Z","pmid":"41490797","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":[]}