{"doi":"10.1101/2025.04.28.650774","title":"Basement Membrane Structural Integrity Dictates Trans-Tissue Deposition of Laminin in Mammals","abstract":"Abstract Basement membranes (BMs) are specialized extracellular matrices (ECMs) essential for tissue structure and function. In non-vertebrates, ECM components can be produced both locally and by distant tissues. In contrast, mammalian ECM has traditionally been considered to originate predominantly from adjacent or tissue-resident cells. The kidney glomerular basement membrane (GBM), composed of laminin-α5β2γ1 and collagen-α3α4α5(IV), is produced by neighboring epithelial cells and functions as a filtration barrier. Alport syndrome, a genetic kidney disease in children, is characterized by GBM structural defects and ectopic laminin-α2 deposition, but the source of this laminin remains unknown. Here, using CRISPR/Cas9 transgenic models, we demonstrated that ectopic laminin-α2 originates not from local kidney cells but from the circulation. Furthermore, laminin-α2 in the mesangium partially derives from circulating sources even under healthy conditions. Our findings uncover a non-cell-autonomous mechanism whereby GBM integrity regulates circulating protein incorporation, revealing a previously unrecognized trans-tissue regulation of BM composition in mammals.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":565051,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"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":1232558,"name":"Meei‐Hua Lin","orcid":"0000-0001-6037-9567","position":1,"is_corresponding":false},{"id":917712,"name":"Pongpratch Puapatanakul","orcid":"0000-0003-0633-5015","position":2,"is_corresponding":false},{"id":422451,"name":"Karen K. McKee","orcid":"0000-0002-2657-5211","position":3,"is_corresponding":false},{"id":1234023,"name":"Hironobu Fujiwara","orcid":"0000-0003-0883-3384","position":4,"is_corresponding":false},{"id":422454,"name":"Peter D. Yurchenco","orcid":"0000-0003-0387-2317","position":5,"is_corresponding":false},{"id":323639,"name":"Jeffrey H. Miner","orcid":"0000-0002-1510-8714","position":6,"is_corresponding":false},{"id":703795,"name":"Kohei Omachi","orcid":"0000-0002-0160-3271","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:56:24.872312Z","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":[]}