{"doi":"10.17615/zvyc-dm09","title":"Inhibition of transforming growth factor-β/Smad signaling improves regeneration of small-for-size rat liver grafts","abstract":"Transforming growth factor-β (TGF-β) is a potent inhibitor of cell proliferation. This study investigated whether overexpression of Smad7, which blocks TGF-β–induced activation of Smad2/3, could prevent the suppression of regeneration of small-for-size liver grafts. Rats were intravenously given adenoviruses (2 × 109 pfu/rat) carrying the LacZ gene or the Smad7 gene (Ad-Smad7) 3 days prior to liver harvesting. Half-size livers were implanted into recipients of the same weight or twice the donor weight, and this resulted in half-size or quarter-size liver grafts. Cell proliferation, detected by 5-bromo-2′-deoxyuridine (BrdU) incorporation, increased to 23% in half-size grafts at 38 hours after implantation but was only 4% in quarter-size grafts. Graft weight did not increase after 38 hours in full-size and quarter-size grafts but increased 28% in half-size grafts. Ad-Smad7 restored BrdU labeling to 32%, and the graft weight increased to 43% in quarter-size grafts. Serum total bilirubin increased approximately 30-fold after the implantation of quarter-size grafts. Ad-Smad7 blunted hyperbilirubinemia by 80%. The basal hepatic TGF-β1 level was 7 ng/g of liver wet weight, and this increased to 30 ng/g at 1.5 hours after the transplantation of full-size grafts but decreased rapidly afterwards. After the transplantation of quarter-size grafts, however, TGF-β1 progressively increased to 159 ng/g in 38 hours. Nuclear phosphorylated Smad2/3 was barely detectable, and p21Cip1 expression was negligible in full-size grafts but increased markedly in quarter-size grafts. Ad-Smad7 blocked Smad2/3 activation and expression of p21Cip1. Together, these data show that TGF-β is responsible, at least in part, for the defective liver regeneration in small-for-size grafts by activating the Smad signaling pathway.","journal":"UNC Libraries","year":2020,"id":136615,"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":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":593496,"name":"Hasibur Rehman","orcid":"0000-0003-1551-6520","position":1,"is_corresponding":false},{"id":539487,"name":"Christopher J. Parsons","orcid":"0000-0001-5741-6937","position":2,"is_corresponding":false},{"id":595774,"name":"Shigeki Tsukada","orcid":null,"position":3,"is_corresponding":false},{"id":593497,"name":"Zhi Zhong","orcid":"0000-0002-2377-0070","position":4,"is_corresponding":false},{"id":540473,"name":"Richard A. Rippe","orcid":null,"position":5,"is_corresponding":false},{"id":232503,"name":"David A. Brenner","orcid":"0000-0003-2573-525X","position":6,"is_corresponding":false},{"id":595775,"name":"Tom P. Theruvath","orcid":null,"position":7,"is_corresponding":false},{"id":342793,"name":"John J. Lemasters","orcid":"0000-0002-7627-6295","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:48.793683Z","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":[]}