{"doi":"10.3390/biom12101531","title":"Molecular Regulation of Heme Oxygenase-1 Expression by E2F Transcription Factor 2 in Lung Fibroblast Cells: Relevance to Idiopathic Pulmonary Fibrosis","abstract":"Idiopathic pulmonary fibrosis (IPF) is a fatal chronic lung disease. Heme oxygenase-1 (HMOX1/HO-1) is an enzyme that catalyzes the degradation of heme. The role of HO-1 in the pathogenesis of IPF has been studied; however, the molecular regulation of HO-1 and its role in IPF are still unclear. In this study, we found that HO-1 protein levels significantly increased in lung myofibroblasts in IPF patients and in lungs in a murine model of bleomycin-induced lung fibrosis. In addition, we observed that administration of a E2F transcription factor inhibitor elevated HO-1 mRNA and protein levels in lung fibroblasts. Downregulation of E2F2 by siRNA transfection increased HO-1 mRNA and protein levels, while overexpression of E2F2 reduced HO-1 levels. However, overexpression of E2F2 did not alter hemin-induced HO-1 protein levels. Furthermore, modulation of HO-1 levels regulated TGF-β1-induced myofibroblast differentiation without altering the phosphorylation of Smad2/3 in lung fibroblast cells. Moreover, the phosphorylation of protein kinase B (Akt) was significantly upregulated in HO-1-depleted lung fibroblast cells. In summary, this study demonstrated that E2F2 regulates the baseline expression of HO-1, but has no effect on modulating HO-1 expression by hemin. Finally, elevated HO-1 expression contributes to the TGF-β1-induced lung myofibroblast differentiation through the activation of the serine/threonine kinase AKT pathway. Overall, our findings suggest that targeting E2F2/HO-1 might be a new therapeutic strategy to treat fibrotic diseases such as IPF.","journal":"Biomolecules","year":2022,"id":274554,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9608,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":514840,"name":"Sarah Taleb","orcid":"0009-0001-2541-8580","position":1,"is_corresponding":false},{"id":898181,"name":"Heather Wang","orcid":"0000-0002-4001-236X","position":2,"is_corresponding":false},{"id":441754,"name":"Narasimham L. Parinandi","orcid":"0000-0003-3489-0286","position":3,"is_corresponding":false},{"id":352759,"name":"Daniel J. Kass","orcid":"0000-0001-6597-7830","position":4,"is_corresponding":false},{"id":237173,"name":"Mauricio Rojas","orcid":"0000-0001-7340-4784","position":5,"is_corresponding":false},{"id":257822,"name":"Cankun Wang","orcid":"0000-0002-0225-9855","position":6,"is_corresponding":false},{"id":235827,"name":"Qin Ma","orcid":"0000-0002-3264-8392","position":7,"is_corresponding":false},{"id":514841,"name":"Jing Zhao","orcid":"0000-0002-0211-9289","position":8,"is_corresponding":false},{"id":404877,"name":"Yutong Zhao","orcid":"0000-0001-6604-9315","position":9,"is_corresponding":false},{"id":515564,"name":"Qinmao Ye","orcid":null,"position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T00:28:12.324621Z","pmid":"36291740","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":[]}