{"doi":"10.1101/2023.02.02.526686","title":"HIV viral protein R induces loss of DCT1-type renal tubules","abstract":"Abstract Hyponatremia and salt wasting is a common occurance in patients with HIV/AIDS, however, the understanding of its contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the expression level of the Slc12a3 gene, encoding the Na-Cl cotransporter, which is responsible for sodium reabsorption in distal nephron segments, we performed single-nucleus RNA sequencing of kidney cortices from three wild-type (WT) and three Vpr-transgenic (Vpr Tg) mice. The results showed that the percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (P < 0.05), and that in Vpr Tg mice, Slc12a3 expression was not different in DCT cell cluster. The Pvalb + DCT1 subcluster had fewer cells in Vpr Tg mice compared with WT (P < 0.01). Immunohistochemistry demonstrated fewer Slc12a3 + Pvalb + DCT1 segments in Vpr Tg mice. Differential gene expression analysis comparing Vpr Tg and WT in the DCT cluster showed Ier3 , an inhibitor of apoptosis, to be the most downregulated gene. These observations demonstrate that the salt-wasting effect of Vpr in Vpr Tg mice is mediated by loss of Slc12a3 + Pvalb + DCT1 segments via apoptosis dysregulation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":402857,"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":0.9601,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":318523,"name":"Teruhiko Yoshida","orcid":"0000-0002-2049-7347","position":1,"is_corresponding":false},{"id":921186,"name":"Shashi Shrivastav","orcid":null,"position":2,"is_corresponding":false},{"id":634440,"name":"Amin Abedini","orcid":"0000-0002-8875-0070","position":3,"is_corresponding":false},{"id":837257,"name":"Jeff Reece","orcid":"0000-0002-0442-1473","position":4,"is_corresponding":false},{"id":469753,"name":"Zeguo Sun","orcid":"0000-0001-5542-2284","position":5,"is_corresponding":false},{"id":270411,"name":"Hewang Lee","orcid":"0000-0003-1338-2573","position":6,"is_corresponding":false},{"id":997409,"name":"Koji Okamoto","orcid":"0000-0001-7587-0164","position":7,"is_corresponding":false},{"id":271933,"name":"Pradeep K. Dagur","orcid":"0000-0002-4491-0853","position":8,"is_corresponding":false},{"id":270414,"name":"Jurgen Heymann","orcid":"0000-0002-6052-4522","position":9,"is_corresponding":false},{"id":228426,"name":"Yongmei Zhao","orcid":"0000-0003-0800-4658","position":10,"is_corresponding":false},{"id":237983,"name":"Joon‐Yong Chung","orcid":"0000-0001-5041-5982","position":11,"is_corresponding":false},{"id":237304,"name":"Stephen M. Hewitt","orcid":"0000-0001-8283-1788","position":12,"is_corresponding":false},{"id":332117,"name":"Pedro A. José","orcid":"0000-0003-1507-7556","position":13,"is_corresponding":false},{"id":289963,"name":"Kyung Lee","orcid":"0000-0002-9756-1765","position":14,"is_corresponding":false},{"id":263575,"name":"John Cijiang He","orcid":"0000-0002-1502-2849","position":15,"is_corresponding":false},{"id":33037,"name":"Cheryl A. Winkler","orcid":"0000-0001-5552-0917","position":16,"is_corresponding":false},{"id":264016,"name":"Mark A. Knepper","orcid":"0000-0002-2276-8091","position":17,"is_corresponding":false},{"id":1180443,"name":"Tomoshige Kino","orcid":"0000-0003-0220-9396","position":18,"is_corresponding":false},{"id":235991,"name":"Avi Z. Rosenberg","orcid":"0000-0003-2356-950X","position":19,"is_corresponding":false},{"id":96238,"name":"Katalin Suszták","orcid":"0000-0002-1005-3726","position":20,"is_corresponding":false},{"id":225761,"name":"Jeffrey B. Kopp","orcid":"0000-0001-9052-186X","position":21,"is_corresponding":false},{"id":445010,"name":"Khun Zaw Latt","orcid":"0000-0001-9754-8723","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:20:32.588152Z","pmid":"36945458","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":[]}