{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T20:57:00Z","timestamp":1783630620645,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T00:00:00Z","timestamp":1513036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81170648"],"award-info":[{"award-number":["81170648"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2018,3]]},"abstract":"Summary<\/jats:title>Cyclophilin D (CypD) is an important component in mitochondrial\u2010dependent tubular cell death in acute kidney injury. However, it is not known whether CypD contributes to tubular cell damage in chronic interstitial fibrosis. We investigated this question in the unilateral ureter obstruction (UUO<\/jats:styled-content>) model of renal interstitial fibrosis. Groups of CypD<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> and wild type (WT<\/jats:styled-content>) mice were killed 7 or 12\u00a0days after UUO<\/jats:styled-content> surgery. The significant tubular cell apoptosis seen in WT UUO<\/jats:styled-content> was significantly reduced in CypD<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> UUO<\/jats:styled-content> based on TUNEL<\/jats:styled-content> and cleaved caspase 3 staining. Other markers of tubular cell damage; loss of E\u2010cadherin and AQP<\/jats:styled-content>1 expression, were also reduced in the CypD<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> UUO<\/jats:styled-content> kidney. This reduced tubular damage was associated with less inflammation and a partial protection against loss of peritubular capillaries. The prominent accumulation of \u03b1\u2010SMA<\/jats:styled-content>+ myofibroblasts and interstitial collagen deposition seen in WT UUO<\/jats:styled-content> was significantly reduced in CypD<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> UUO<\/jats:styled-content> on day 12, but not day 7. Activation of several pro\u2010fibrotic signalling pathways (p38 MAPK<\/jats:styled-content>, JNK<\/jats:styled-content> and Smad3) was unaltered in CypD<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> UUO<\/jats:styled-content>, arguing that CypD acts independently to promote renal fibrosis. CypD<\/jats:italic> deletion in cultured tubular cells attenuated oxidative stress\u2010induced pro\u2010inflammatory, pro\u2010fibrotic and apoptotic responses; however, responses to angiotensin II<\/jats:styled-content> and LPS<\/jats:styled-content> were unaffected. In contrast, CypD<\/jats:italic> deletion in cultured renal fibroblasts did not affect PDGF<\/jats:styled-content>\u2010induced proliferation or TGF<\/jats:styled-content>\u2010\u03b21\u2010induced collagen I expression, suggesting no direct role of CypD in the fibroblast response. In conclusion, we have identified a role for CypD in chronic tubular cell damage and in the development of renal interstitial fibrosis.<\/jats:p>","DOI":"10.1111\/1440-1681.12881","type":"journal-article","created":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T08:12:55Z","timestamp":1513066375000},"page":"250-260","source":"Crossref","is-referenced-by-count":22,"title":["Cyclophilin D promotes tubular cell damage and the development of interstitial fibrosis in the obstructed kidney"],"prefix":"10.1111","volume":"45","author":[{"given":"Weiping","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Nephrology Xinqiao Hospital Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khai G","family":"Leong","sequence":"additional","affiliation":[{"name":"Department of Nephrology Monash Health Monash Medical Centre Clayton Victoria Australia"},{"name":"Monash University Centre for Inflammatory Diseases Monash Medical Centre Clayton Victoria 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