{"doi":"10.14814/phy2.15468","title":"Meprin β expression modulates the interleukin‐6 mediated <scp>JAK2‐STAT3</scp> signaling pathway in ischemia/reperfusion‐induced kidney injury","abstract":"Meprin metalloproteinases have been implicated in the pathophysiology of ischemia/reperfusion (IR)-induced kidney injury. Previous in vitro data showed that meprin β proteolytically processes interleukin-6 (IL-6) resulting in its inactivation. Recently, meprin-β was also shown to cleave the IL-6 receptor. The goal of this study was to determine how meprin β expression impacts IL-6 and downstream modulators of the JAK2-STAT3-mediated signaling pathway in IR-induced kidney injury. IR was induced in 12-week-old male wild-type (WT) and meprin β knockout (βKO) mice and kidneys obtained at 24 h post-IR. Real-time PCR, western blot, and immunostaining/microscopy approaches were used to quantify mRNA and protein levels respectively, and immunofluorescence counterstaining with proximal tubule (PT) markers to determine protein localization. The mRNA levels for IL-6, CASP3 and BCL-2 increased significantly in both genotypes. Interestingly, western blot data showed increases in protein levels for IL-6, CASP3, and BCL-2 in the βKO but not in WT kidneys. However, immunohistochemical data showed increases in IL-6, CASP3, and BCL-2 proteins in select kidney tubules in both genotypes, shown to be PTs by immunofluorescence counterstaining. IR-induced increases in p-STAT-3 and p-JAK-2 in βKO at a global level but immunoflourescence counterstaining demonstrated p-JAK2 and p-STAT3 increases in select PT for both genotypes. BCL-2 increased only in the renal corpuscle of WT kidneys, suggesting a role for meprins expressed in leukocytes. Immunohistochemical analysis confirmed higher levels of leukocyte infiltration in WT kidneys when compared to βKO kidneys. The present data demonstrate that meprin β modulates IR-induced kidney injury in part via IL-6/JAK2/STAT3-mediated signaling.","journal":"Physiological Reports","year":2022,"id":277003,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"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":948579,"name":"Faihaa Ahmed","orcid":null,"position":1,"is_corresponding":false},{"id":948580,"name":"Ayman Abouzeid","orcid":null,"position":2,"is_corresponding":false},{"id":947982,"name":"Elimelda Moige Ongeri","orcid":"0000-0002-2963-4379","position":3,"is_corresponding":false},{"id":947981,"name":"Shaymaa Abousaad","orcid":"0000-0002-4344-9217","position":0,"is_corresponding":true}],"reference_count":104,"raw_metadata":null,"created_at":"2026-07-19T00:28:34.768552Z","pmid":"36117389","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":[]}