{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:47:40Z","timestamp":1791204460057,"version":"4.2.0"},"reference-count":37,"publisher":"S. Karger AG","issue":"1-2","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"published-print":{"date-parts":[[2011]]},"abstract":"<i>Background\/Aims:<\/i> Fluorofenidone [1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone, AKF-PD], a novel pyridone agent, showed potent antifibrotic properties. The aim of the present study was to investigate the effects of AKF-PD on diabetic nephropathy and kidney fibrosis, and to obtain an insight into its mechanisms of action. <i>Methods:<\/i> We administered AKF-PD to diabetic <i>db\/db <\/i>mice for 12 weeks. Moreover, we performed in vitro cultures using murine mesangial cells exposed to high ambient glucose concentrations. <i>Results:<\/i> AKF-PD reduced renal hypertrophy, mesangial matrix expansion and albuminuria in the <i>db\/db<\/i> mice. The upregulated expression of \u03b1<sub>1<\/sub>(I)- and \u03b1<sub>1<\/sub>(IV)-collagen and fibronectin mRNAs, transforming growth factor-\u03b21 (TGF-\u03b2<sub>1<\/sub>), \u03b1-smooth muscle actin (\u03b1-SMA), and tissue inhibitors of metalloproteinase 1 (TIMP-1) mRNAs and proteins was inhibited by AKF-PD treatment in the renal cortex of <i>db<\/i>\/<i>db<\/i> mice. The maximal effective dose of AKF-PD was about 500 mg\/kg body weight. AKF-PD inhibited the upregulated expression of \u03b1<sub>1<\/sub>(I)- and \u03b1<sub>1<\/sub>(IV)-collagens, TGF-\u03b2<sub>1<\/sub>, TIMP-1 and \u03b1-SMA induced by high glucose concentrations in cultured mesangial cells. <i>Conclusions:<\/i> Our data indicate that AKF-PD diminishes the abnormal accumulation of mesangial matrix through the inhibition of upregulated expression of TGF-\u03b2 target genes in kidneys of <i>db\/db <\/i>mice, resulting in attenuation of renal fibrosis and amelioration of renal dysfunction despite persistent hyperglycemia. Therefore, AKF-PD, a potent antifibrotic agent, holds great promise in the treatment of diabetic nephropathy.<\/jats:p>","DOI":"10.1159\/000329419","type":"journal-article","created":{"date-parts":[[2011,8,16]],"date-time":"2011-08-16T08:34:09Z","timestamp":1313483649000},"page":"88-99","source":"Crossref","is-referenced-by-count":29,"title":["Fluorofenidone Attenuates Diabetic Nephropathy and Kidney Fibrosis in <i>db\/db<\/i> Mice"],"prefix":"10.1159","volume":"88","author":[{"given":"Ling Hao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Shi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang Bin","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong Jing","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang Fang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang Zhe","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao Miao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren Na","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao Yun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao He","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Jian","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2011,8,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1753-0407.2009.00037.x"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.2174%2F157339910793360851"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1681%2FASN.2009070737"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1097%2F01.ASN.0000065640.77499.D7"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.3181%2F0705-MR-134"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1055%2Fs-0029-1220752"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1097%2F01.ASN.0000133198.74973.60"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1152%2Fajprenal.90613.2008"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1159%2F000256659"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016%2FS0006-291X%2802%2902708-0"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1152%2Fajprenal.00043.2008"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1152%2Fajprenal.00357.2005"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.ki.5002717"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1021%2Fjf9040723"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1053%2Fj.ajkd.2009.11.021"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038%2Fsj.bjp.0704131"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jss.2004.12.007"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1681%2FASN.2008090931"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.2215%2FCJN.01050207"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1440-1797.2009.01129.x"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016%2FS0092-8674%2800%2981294-5"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1126%2Fscience.153.3740.1127"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016%2FS0002-9440%2810%2962473-X"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1681%2FASN.2004110915"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.2337%2Fdiabetes.53.1.166"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.2337%2Fdb06-1134"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1152%2Fajprenal.00357.2005"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016%2FS0002-9440%2810%2964121-1"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.jchromb.2006.01.010"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1681%2FASN.2008090931"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1097%2F01.ASN.0000065640.77499.D7"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1042%2FBJ20082277"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1016%2FS0167-4838%2899%2900279-4"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1016%2FS0002-9440%2810%2964121-1"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.120055097"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1093%2Fndt%2Fgfl598"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1097%2F01.ASN.0000064500.89551.76"}],"container-title":["Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/329419","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/329419","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T18:19:39Z","timestamp":1745432379000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000329419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011]]},"references-count":37,"journal-issue":{"issue":"1-2","published-online":{"date-parts":[[2011,9,1]]},"published-print":{"date-parts":[[2011,9,7]]}},"URL":"https:\/\/doi.org\/10.1159\/000329419","archive":["Portico"],"relation":{},"ISSN":["0031-7012","1423-0313"],"issn-type":[{"value":"0031-7012","type":"print"},{"value":"1423-0313","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011]]}}}