{"doi":"10.1101/2021.04.15.440011","title":"TAZ/TEAD complex regulates TGF-β1-mediated fibrosis in iPSC-derived renal organoids","abstract":"Abstract Chronic kidney disease (CKD) progresses by replacement of functional tissue compartments with fibrosis, representing a maladaptive repair process. Shifting kidney repair towards a physiologically-intact architecture, rather than fibrosis, is key to blocking CKD progression. In this study, we developed a fibrosis model that uses human induced pluripotent stem cell (iPSC)-based three-dimensional renal organoids, in which exogenous TGF-β1 induces production of extracellular matrix. In these organoids, TGF- β1 increased transcription factor tafazzin (TAZ) expression. Further, in human kidney biopsies, nuclear TAZ expression was markedly increased in mild and moderate fibrosis. In cultured renal tubular cells expressing a fibrogenic program, TAZ formed a trimeric complex with phosphorylated mothers against decapentaplegic homolog 3 (p-SMAD3) and TEA domain protein (TEAD)-4. Overexpression of TEAD4 protein suppressed collagen-1α1 ( COL1A1 ) promoter activity, and expression of TAZ attenuated this inhibition. INT-767, a dual bile acid receptor agonist binding farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5), decreased the TGF-β1-induced increase in p-SMAD3 and TAZ, and preserved renal organoid architecture. These data demonstrate, in an iPSC-derived renal organoid fibrosis model, that INT767 prevents fibrosis programs early in the course of tubular injury through modulation of the TEAD4/TAZ pathway.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220625,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":336792,"name":"Marco Delsante","orcid":"0000-0003-0715-6764","position":1,"is_corresponding":false},{"id":406755,"name":"Parnaz Daneshpajouhnejad","orcid":"0000-0002-8845-5813","position":2,"is_corresponding":false},{"id":399546,"name":"Paride Fenaroli","orcid":"0000-0001-8019-4754","position":3,"is_corresponding":false},{"id":235988,"name":"Kira A. Perzel Mandell","orcid":"0000-0001-6262-6904","position":4,"is_corresponding":false},{"id":344473,"name":"Xiaoxin X. Wang","orcid":"0000-0001-9205-6228","position":5,"is_corresponding":false},{"id":281040,"name":"Shogo Takahashi","orcid":"0000-0002-3831-5353","position":6,"is_corresponding":false},{"id":235989,"name":"Marc K. Halushka","orcid":"0000-0002-7112-7389","position":7,"is_corresponding":false},{"id":225761,"name":"Jeffrey B. Kopp","orcid":"0000-0001-9052-186X","position":8,"is_corresponding":false},{"id":281043,"name":"Moshe Levi","orcid":"0000-0001-6403-2261","position":9,"is_corresponding":false},{"id":235991,"name":"Avi Z. Rosenberg","orcid":"0000-0003-2356-950X","position":10,"is_corresponding":false},{"id":768127,"name":"Xiaoping Yang","orcid":"0000-0003-1263-2710","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T23:53:46.965811Z","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":[]}