{"doi":"10.1038/s41598-021-89983-x","title":"DHHC21 deficiency attenuates renal dysfunction during septic injury","abstract":"Abstract Renal dysfunction is one of the most common complications of septic injury. One critical contributor to septic injury-induced renal dysfunction is renal vascular dysfunction. Protein palmitoylation serves as a novel regulator of vascular function. Here, we examined whether palmitoyl acyltransferase (PAT)-DHHC21 contributes to septic injury-induced renal dysfunction through regulating renal hemodynamics. Multispectral optoacoustic imaging showed that cecal ligation and puncture (CLP)-induced septic injury caused impaired renal excretion, which was improved in DHHC21 functional deficient ( Zdhhc21 dep/dep ) mice. DHHC21 deficiency attenuated CLP-induced renal pathology, characterized by tissue structural damage and circulating injury markers. Importantly, DHHC21 loss-of-function led to better-preserved renal perfusion and oxygen saturation after CLP. The CLP-caused reduction in renal blood flow was also ameliorated in Zdhhc21 dep/dep mice. Next, CLP promoted the palmitoylation of vascular α1-adrenergic receptor (α1AR) and the activation of its downstream effector ERK, which were blunted in Zdhhc21 dep/dep mice. Vasoreactivity analysis revealed that renal arteries from Zdhhc21 dep/dep mice displayed reduced constriction response to α1AR agonist phenylephrine compared to those from wild-type mice. Consistently, inhibiting PATs with 2-bromopalmitate caused a blunted vasoconstriction response to phenylephrine in small arteries isolated from human kidneys. Therefore, DHHC21 contributes to impaired renal perfusion and function during septic injury via promoting α1AR palmitoylation-associated vasoconstriction.","journal":"Scientific Reports","year":2021,"id":181890,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9624,"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":472153,"name":"Ethan Zheng","orcid":null,"position":1,"is_corresponding":false},{"id":321687,"name":"Yonggang Ma","orcid":"0000-0003-1711-0639","position":2,"is_corresponding":false},{"id":357390,"name":"Victor Chatterjee","orcid":null,"position":3,"is_corresponding":false},{"id":331333,"name":"Nuria Villalba","orcid":"0000-0001-5903-2937","position":4,"is_corresponding":false},{"id":471920,"name":"Jerome W. Breslin","orcid":"0000-0003-4867-3151","position":5,"is_corresponding":false},{"id":720290,"name":"Ruisheng Liu","orcid":"0000-0002-2220-1888","position":6,"is_corresponding":false},{"id":357391,"name":"Mack H. Wu","orcid":null,"position":7,"is_corresponding":false},{"id":332925,"name":"Sarah Y. Yuan","orcid":null,"position":8,"is_corresponding":false},{"id":355848,"name":"Xiaoyuan Yang","orcid":"0000-0002-2769-0000","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T23:48:09.223560Z","pmid":"34045489","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":[]}