{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T11:32:58Z","timestamp":1770550378648,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T00:00:00Z","timestamp":1520467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Angiotensin\u2010converting enzyme inhibitors (ACEi) are widely used to deter the progression of chronic kidney disease (CKD). Besides controlling hypertension and reduction of intra\u2010glomerular pressure, ACEi appear to have anti\u2010fibrotic effects in the renal cortex. N\u2010acetyl\u2010seryl\u2010aspartyl\u2010lysyl\u2010proline (Ac\u2010SDKP), an endogenous tetrapeptide that is degraded by ACE, has also been shown to ameliorate the pro\u2010fibrotic phenotype displayed in CKD in our recent study. Whether the anti\u2010fibrotic properties of ACEi are mediated by Ac\u2010SDKP has not been fully investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To delineate the role of Ac\u2010SDKP in ACE blockade, 12\u2010week\u2010old male BALB\/c mice underwent sham operation or unilateral ureteric obstruction (UUO). UUO mice were subjected to: (i) vehicle; (ii) captopril or (iii) captopril in conjunction with S17092, a prolyl oligopeptidase inhibitor. After 7\u00a0days, mice were sacrificed and kidneys harvested for analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After UUO, there were heightened expressions of collagen I, collagen III, fibronectin and \u03b1\u2010SMA associated with significant levels of tubulointerstitial injury on histological examination. Furthermore, p44\/42 mitogen\u2010activated protein kinase (MAPK) and transforming growth factor beta 1(TGF\u2010\u03b21) signalling were upregulated. These were significantly ameliorated by captopril treatment alone but unaffected by co\u2010administration of captopril with S17092. Captopril treatment had resulted in elevated urinary Ac\u2010SDKP levels, an effect that was eliminated by the co\u2010administration with S17092.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study allowed the investigation of the renoprotective property of ACEi in the absence of Ac\u2010SDKP and proved conclusively that Ac\u2010SDKP is the prime anti\u2010fibrotic mediator of captopril, acting via p44\/42 MAPK and TGF\u2010\u03b21 signalling pathways. Future research to expand CKD armamentarium should explore the utility of augmenting Ac\u2010SDKP levels.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nep.13000","type":"journal-article","created":{"date-parts":[[2017,1,11]],"date-time":"2017-01-11T13:11:49Z","timestamp":1484140309000},"page":"297-307","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["N\u2010acetyl\u2010seryl\u2010aspartyl\u2010lysyl\u2010proline mediates the anti\u2010fibrotic properties of captopril in unilateral ureteric obstructed BALB\/C mice"],"prefix":"10.1111","volume":"23","author":[{"given":"Gary C.W.","family":"Chan","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine The University of Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao Jia","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine The University of Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kam Wa","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine The University of Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wai Han","family":"Yiu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine The University of Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ailis","family":"Zou","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine The University of Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao Ru","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, and Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui Yao","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, and Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kar Neng","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine The University of Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sydney C.W.","family":"Tang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine The University of Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2005.07.011"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)11445-8"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfu411"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.14.1411"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.3.779"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000126172.01673.84"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(90)90489-A"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.2.794"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000258406.66954.4f"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.144568"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005040385"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.3.838"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000346116"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2012.07.023"},{"key":"e_1_2_7_16_1","first-page":"795","article-title":"N\u2010acetyl\u2010seryl\u2010aspartyl\u2010lysyl\u2010proline attenuates renal inflammation and tubulointerstitial fibrosis in rats","volume":"26","author":"Wang M","year":"2010","journal-title":"Int. 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