{"doi":"10.1016/j.taap.2025.117465","title":"Hepatocyte mitochondrial DNA activated store-operated Ca2+ entry via Stim1/Orai1-induced podocyte injury in trichloroethylene sensitized mice: A new insight in liver and kidney crosstalk","abstract":null,"journal":"Toxicology and Applied Pharmacology","year":2025,"id":597086,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1529471,"name":"Xue-qian Jia","orcid":null,"position":1,"is_corresponding":false},{"id":1529472,"name":"Hai-bo Xie","orcid":null,"position":2,"is_corresponding":false},{"id":1529473,"name":"Li-fu Zhu","orcid":null,"position":3,"is_corresponding":false},{"id":1529474,"name":"Peng-cheng Zhou","orcid":null,"position":4,"is_corresponding":false},{"id":1529475,"name":"Rui-xuan Cheng","orcid":null,"position":5,"is_corresponding":false},{"id":1529476,"name":"Chun-lin Cao","orcid":null,"position":6,"is_corresponding":false},{"id":1529477,"name":"Qi-xing Zhu","orcid":null,"position":7,"is_corresponding":false},{"id":1529478,"name":"Jia-xiang Zhang","orcid":null,"position":8,"is_corresponding":false},{"id":1529470,"name":"Luo-lun Dong","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Hepatocyte mitochondrial DNA activated store-operated Ca2+ entry via Stim1/Orai1-induced podocyte injury in trichloroethylene sensitized mice: A new insight in liver and kidney crosstalk","abstract":"Previous clinical case studies revealed that patients with severe liver damage often develop kidney damage in occupational medicamentose-like dermatitis due to trichloroethylene (OMDT). However, the mechanism of this crosstalk is unknown. In this study, we extracted hepatocyte mtDNA from TCE-sensitized positive mice and co-treated it with a mouse podocyte line, MPC5. The expression of the stromal interaction molecule 1 (Stim1) and calcium release-activated calcium channel protein 1 (Orai1) proteins did not change significantly with or without interference with the Stimulator of interferon gene (STING) protein in hepatocyte mtDNA pretreated MPC5 cells. Subsequently, siRNA interference treatment of Stim1 and Orai1, respectively, was found to significantly ameliorate the damage to podocytes. Moreover, lentiviral transfection for overexpression of the key protein Orai1 was carried out, and the expression of inflammatory factors was significantly elevated. In animal experiments, the SOCE inhibitor YM-58483 was used to treat TCE-sensitized mice, and the administration of YM-58483 alleviated the reduction in the expression of podocyte injury proteins. In summary, this study explored the role of hepatocyte mtDNA-mediated podocyte injury in Ca<sup>2+</sup> signaling pathway activation and immune kidney injury in TCE sensitization-positive mice. We found that hepatocyte mtDNA enhances SOCE by increasing the interaction between Orai1 and Stim1 and that SOCE activation mediated by hepatocyte mtDNA processing regulates the secretion of inflammatory factors by podocytes. SOCE inhibitors reversed this phenomenon and mitigated immune kidney damage caused by TCE sensitization. This study provides new insight into the mechanisms of renal damage in liver and kidney crosstalk induced by TCE sensitization.","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40669774","pmcid":null,"openalex_id":"https://openalex.org/W4412434135","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"82304106","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82273602","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82173494","title":null},{"funder_name":"Ministry of Education of the People&apos;s Republic of China","grant_id":"AYPYS-2023-5","title":null},{"funder_name":"Ministry of Education of the People&apos;s Republic of China","grant_id":"AYPYS-2024-4","title":null},{"funder_name":"Anhui Provincial Department of Education","grant_id":"JWFX2023007","title":null},{"funder_name":"Anhui Medical University","grant_id":"","title":null}],"total_grants":7,"fwci":1.6177,"citation_percentile":0.80670754,"influential_citations":0,"citation_trend":[{"year":2026,"count":2}],"oa_status":"closed","license":"https://doi.org/10.15223/policy-004","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0041008X25002418?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0041008X25002418?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.taap.2025.117465","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40669774","host_type":"repository"}],"fields_of_study":["Ion Channels and Receptors","Cardiovascular, Neuropeptides, and Oxidative Stress Research","Dietary Effects on Health"],"mesh_terms":["Stromal Interaction Molecule 1","ORAI1 Protein","Animals","Calcium","Cell Line","DNA, Mitochondrial","Kidney","Liver","Male","Trichloroethylene","Calcium Signaling","Hepatocytes","Podocytes","Mice"],"keywords":["ORAI1","Hepatocyte","Podocyte","Crosstalk","Cell biology","STIM1","Liver injury","Chemistry","Trichloroethylene","Kidney","Biology","Endocrinology","Biochemistry","Endoplasmic reticulum","Liver","Mitochondrial DNA"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T12:12:04.744039Z","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":[]}