{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:58:18Z","timestamp":1790909898416,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,1,6]],"date-time":"2019-01-06T00:00:00Z","timestamp":1546732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2014R1A2A2A01004731"],"award-info":[{"award-number":["2014R1A2A2A01004731"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017M3A9B4032528"],"award-info":[{"award-number":["2017M3A9B4032528"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although it is known that the expression and activity of sirtuin 1 (Sirt1) decrease in the aged kidney, the role of interaction between Sirt1 and hypoxia\u2010inducible factor (HIF)\u20101\u03b1 is largely unknown. In this study, we investigated whether HIF\u20101\u03b1 could be a deacetylation target of Sirt1 and the effect of their interaction on age\u2010associated renal injury. Five\u2010week\u2010old (young) and 24\u2010month\u2010old (old) C57Bl\/6J mice were assessed for their age\u2010associated changes. Kidneys from aged mice showed increased infiltration of CD68\u2010positive macrophages, higher expression of extracellular matrix (ECM) proteins, and more apoptosis than young controls. They also showed decreased Sirt1 expression along with increased acetylated HIF\u20101\u03b1. The level of Bcl\u20102\/adenovirus E1B\u2010interacting protein 3, carbonic anhydrase 9, Snail, and transforming growth factor\u2010\u03b21, which are regulated by HIF\u20101\u03b1, was significantly higher in aged mice suggesting that HIF\u20101\u03b1 activity was increased. In HK\u20102 cells, Sirt1 inhibitor sirtinol and siRNA\u2010mediated knockdown of Sirt1 enhanced apoptosis and ECM accumulation. During hypoxia, Sirt1 was down\u2010regulated, which allowed the acetylation and activation of HIF\u20101\u03b1. Resveratrol, a Sirt1 activator, effectively prevented hypoxia\u2010induced production of ECM proteins, mitochondrial damage, reactive oxygen species generation, and apoptosis. The inhibition of HIF\u20101\u03b1 activity by Sirt1\u2010induced deacetylation of HIF\u20101\u03b1 was confirmed by Sirt1 overexpression under hypoxic conditions and by resveratrol treatment or Sirt1 overexpression in HIF\u20101\u03b1\u2010transfected HK\u20102 cells. Finally, we confirmed that chronic activation of HIF\u20101\u03b1 promoted apoptosis and fibrosis, using tubular cell\u2010specific HIF\u20101\u03b1 transgenic mice. Taken together, our data suggest that Sirt1\u2010induced deacetylation of HIF\u20101\u03b1 may have protective effects against tubulointerstitial damage in aged kidney.<\/jats:p>","DOI":"10.1111\/acel.12904","type":"journal-article","created":{"date-parts":[[2019,1,7]],"date-time":"2019-01-07T03:08:50Z","timestamp":1546830530000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["Sirt1\u2013hypoxia\u2010inducible factor\u20101\u03b1 interaction is a key mediator of tubulointerstitial damage in the aged kidney"],"prefix":"10.1111","volume":"18","author":[{"given":"Dong Ryeol","family":"Ryu","sequence":"first","affiliation":[{"name":"School of Medicine Ewha Womans University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Ra","family":"Yu","sequence":"additional","affiliation":[{"name":"Hyonam Kidney Laboratory Soon Chun Hyang University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung Hye","family":"Kong","sequence":"additional","affiliation":[{"name":"School of Medicine Ewha Womans University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyoungnae","family":"Kim","sequence":"additional","affiliation":[{"name":"Hyonam Kidney Laboratory Soon Chun Hyang University Seoul Korea"},{"name":"Department of Internal Medicine Soon Chun Hyang University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon Hyo","family":"Kwon","sequence":"additional","affiliation":[{"name":"Hyonam Kidney Laboratory Soon Chun Hyang University Seoul Korea"},{"name":"Department of Internal Medicine Soon Chun Hyang University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Seok","family":"Jeon","sequence":"additional","affiliation":[{"name":"Hyonam Kidney Laboratory Soon Chun Hyang University Seoul Korea"},{"name":"Department of Internal Medicine Soon Chun Hyang University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Cheol","family":"Han","sequence":"additional","affiliation":[{"name":"Hyonam Kidney Laboratory Soon Chun Hyang University Seoul Korea"},{"name":"Department of Internal Medicine Soon Chun Hyang University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1904-1684","authenticated-orcid":false,"given":"Hyunjin","family":"Noh","sequence":"additional","affiliation":[{"name":"Hyonam Kidney Laboratory Soon Chun Hyang University Seoul Korea"},{"name":"Department of Internal Medicine Soon Chun Hyang University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.05.026"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005121302"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019194"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.16.9082"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1602264113"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2011.104"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023566"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890701408194"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1169956"},{"issue":"8","key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1681\/ASN.V781106","article-title":"Aging and the kidney","volume":"7","author":"Epstein M.","year":"1996","journal-title":"Journal of the American Society of Nephrology"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2008.03.012"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2013.09.026"},{"issue":"4","key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1681\/ASN.V134894","article-title":"Role of high glucose\u2010induced nuclear factor\u2010\u03baB activation in monocyte chemoattractant protein\u20101 expression by mesangial cells","volume":"13","author":"Ha H.","year":"2002","journal-title":"Journal of the American Society of Nephrology"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.067728"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41563"},{"issue":"12","key":"e_1_2_8_17_1","first-page":"3810","article-title":"Hypoxia promotes fibrogenesis in vivo via HIF\u20101 stimulation of epithelial\u2010to\u2010mesenchymal transition","volume":"117","author":"Higgins D. 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