{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:49:11Z","timestamp":1782996551751,"version":"3.54.5"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019492","name":"National Natural Science Foundation of China-China Academy of General Technology Joint Fund for Basic Research","doi-asserted-by":"publisher","award":["81170689, 81570677 , 81873622"],"award-info":[{"award-number":["81170689, 81570677 , 81873622"]}],"id":[{"id":"10.13039\/501100019492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Renal ischemia\u2013reperfusion (IR) injury and cyclosporine A (CsA) nephrotoxicity affect allograft function and survival. The prolonged effects and underlying mechanisms of erythropoietin derived cyclic helix B peptide (CHBP) and\/or caspase-3 small interfering RNA (CASP-3siRNA) were investigated in mouse kidneys, as well as kidney epithelial cells (TCMK-1), subjected to transplant-related injuries. Bilateral renal pedicles were clamped for 30\u00a0min followed by reperfusion for 2 and 8 weeks, with\/without 35 mg\/kg CsA gavage daily and\/or 24 nmol\/kg CHBP intraperitoneal injection every 3 days. The ratio of urinary albumin to creatinine was raised by IR injury, further increased by CsA and lowered by CHBP at 2, 4, 6 and 8 weeks, whereas the level of SCr was not significantly affected. Similar change trends were revealed in tubulointerstitial damage and fibrosis, HMGB1 and active CASP-3 protein. Increased apoptotic cells in IR kidneys were decreased by CsA and CHBP at 2 and\/or 8 weeks. p70 S6 kinase and mTOR were reduced by CsA with\/without CHBP at 2 weeks, so were S6 ribosomal protein and GSK-3\u03b2 at 8 weeks, with reduced CASP-3 at both time points. CASP-3 was further decreased by CHBP in IR or IR + CsA kidneys at 2 or 8 weeks. Furthermore, in TCMK-1 cells CsA induced apoptosis was decreased by CHBP and\/or CASP-3siRNA treatment. Taken together, CHBP predominantly protects kidneys against IR injury at 2 weeks and\/or CsA nephrotoxicity at 8 weeks, with different underlying mechanisms. Urinary albumin\/creatinine is a good biomarker in monitoring the progression of transplant-related injuries. CsA divergently affects apoptosis in kidneys and cultured kidney epithelial cells, in which CHBP and\/or CASP-3siRNA reduces inflammation and apoptosis.<\/jats:p>","DOI":"10.3389\/fimmu.2021.697751","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T08:29:41Z","timestamp":1627288181000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Long-Term Protection of CHBP Against Combinational Renal Injury Induced by Both Ischemia\u2013Reperfusion and Cyclosporine A in 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