{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:23:10Z","timestamp":1769602990914,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":303,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:p><jats:bold>Background and purpose:<\/jats:bold> Rhein, an anthraquinone compound isolated from rhubarb, has been proved effective in treatment of experimental diabetic nephropathy (DN). To explore the mechanism of its therapeutic effect on DN, rhein was tested for its effect on the hexosamine pathway.<\/jats:p><jats:p><jats:bold>Experimental approach<\/jats:bold>: The influence of rhein on cellular hypertrophy, fibronectin synthesis, glucose uptake, glutamine: fructose 6\u2010phosphate aminotransferase (GFAT) activity, UDP\u2010N\u2010acetylglucosamine (UDP\u2010GlcNAc) level and TGF\u2010\u03b21 and p21 expression was evaluated in MCGT1 cells, a GLUT1 transgenic rat mesangial cell line. GFAT activity in normal rat mesangial cells in high glucose concentrations and <jats:italic>in vitro<\/jats:italic> was also measured.<\/jats:p><jats:p><jats:bold>Key results<\/jats:bold>: Significantly increased fibronectin synthesis, cellular hypertrophy, much higher GFAT activity and UDP\u2010GlcNAc level and increased TGF\u2010\u03b21 and p21 expression were found in MCGT1 cells cultured in normal glucose concentration. Rhein treatment decreased all these features of MCGT1 cells but did not exert a direct effect on GFAT enzymatic activity.<\/jats:p><jats:p><jats:bold>Conclusions and implications:<\/jats:bold> There was over\u2010activity of the hexosamine pathway in MCGT1 cells, which may explain the higher expression of TGF\u2010\u03b21 and p21, the cellular hypertrophy and the increased expression of extracellular matrix (ECM) components in the cells. By inhibiting the increased activity the hexosamine pathway, rhein decreased TGF\u2010\u03b21 and p21 expression and thus contributed to the decreased cellular hypertrophy and ECM synthesis. Inhibition of the hexosamine pathway may be one of the mechanism through which rhein exerts its therapeutic role in diabetic nephropathy.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2008) <jats:bold>153<\/jats:bold>, 1456\u20131464; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.26\">10.1038\/bjp.2008.26<\/jats:ext-link>; published online 11 February 2008<\/jats:p>","DOI":"10.1038\/bjp.2008.26","type":"journal-article","created":{"date-parts":[[2008,2,11]],"date-time":"2008-02-11T10:59:26Z","timestamp":1202727566000},"page":"1456-1464","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Rhein reverses the diabetic phenotype of mesangial cells over\u2010expressing the glucose transporter (GLUT1) by inhibiting the hexosamine pathway"],"prefix":"10.1111","volume":"153","author":[{"given":"J\u2010M","family":"Zheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u2010M","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u2010S","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z\u2010H","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"F185","article-title":"Increased extracellular matrix synthesis and mRNA in mesangial cells grown in high\u2010glucose medium","volume":"260","author":"Ayo SH","year":"1991","journal-title":"Am J Physiol"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/1043-6618(90)90725-S"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/414813a","article-title":"Biochemistry and molecular cell biology of diabetic complications","volume":"414","author":"Browniee M","year":"2001","journal-title":"Nature"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20690"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001813-199306000-00019"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001049200"},{"key":"e_1_2_7_8_1","first-page":"427","article-title":"Regulation of glutamine:fructose\u20106\u2010phosphate amidotransferase activity by high glucose and transforming growth factor beta in rat mesangial cells","volume":"48","author":"Crook ED","year":"2000","journal-title":"J Investig Med"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119390"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118876"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118226"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.46.6.1030"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000011"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00438.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.281.1.F151"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-981469"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119875"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1983.40"},{"key":"e_1_2_7_19_1","first-page":"61","article-title":"Effect of emodin on c\u2010myc proto\u2010oncogen expression in cultured rat mesangial cells","volume":"17","author":"Liu ZH","year":"1996","journal-title":"Acta Pharmacol Sin"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfg288"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/039463200702000106"},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1016\/S0021-9258(19)67706-9","article-title":"Discovery of a metabolic pathway mediating glucose\u2010induced desensitization of the glucose transport system: role of hexosamine biosynthesis in the induction of insulin resistance","volume":"266","author":"Marshall S","year":"1991","journal-title":"J Biol Chem"},{"issue":"2","key":"e_1_2_7_23_1","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1042\/BJ20041506","article-title":"Glucosamine induces cell\u2010cycle arrest and hypertrophy of mesangial cells: implication of gangliosides","volume":"388","author":"Masson E","year":"2005","journal-title":"Biochem J"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540600755980"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111523"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.8.1003"},{"key":"e_1_2_7_27_1","first-page":"1507","article-title":"Effect of lonidamine and rhein on the phosphorylation potential generated by respiring rat liver mitochondria","volume":"13","author":"Miccadei S","year":"1993","journal-title":"Anticancer Res"},{"key":"e_1_2_7_28_1","first-page":"101","article-title":"The relationship between glucose control and the development of diabetic nephropathy in type I diabetes","volume":"17","author":"Molitch ME","year":"1997","journal-title":"Semin Nephrol"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215258"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00193.x"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.136.7.2809"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.8.1562"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-002-0123-1"},{"key":"e_1_2_7_34_1","first-page":"63","article-title":"Insulin stimulation of glutamine: fructose\u20106\u2010phosphate amidotransferase occurs via an insulin\u2010like growth factor\u20101 pathway in rat fibroblasts","volume":"104","author":"Simmons ST","year":"1999","journal-title":"Res Commun Mol Pathol Pharmacol"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOMG.0000023585.95430.f4"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.9.1492"},{"key":"e_1_2_7_37_1","doi-asserted-by":"crossref","first-page":"10148","DOI":"10.1016\/S0021-9258(18)99202-1","article-title":"Coordinated regulation of glutamine:fructose\u20106\u2010phosphate amidotransferase activity by insulin, glucose, and glutamine: role of hexosamine biosynthesis in enzyme regulation","volume":"266","author":"Traxinger RR","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.157"},{"issue":"3","key":"e_1_2_7_39_1","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1042\/bj3160985","article-title":"Expression of extracellular matrix molecules in human mesangial cells in response to prolonged hyperglycaemia","volume":"316","author":"Wahab NA","year":"1996","journal-title":"Biochem J"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8227(94)90096-5"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1992.330"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.07710.x"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbbm.2003.02.001"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00901.x"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00189.2001"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fbjp.2008.26","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fbjp.2008.26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/bjp.2008.26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T17:42:59Z","timestamp":1697132579000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/bjp.2008.26"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,4]]},"references-count":44,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2008,4]]}},"alternative-id":["10.1038\/bjp.2008.26"],"URL":"https:\/\/doi.org\/10.1038\/bjp.2008.26","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,4]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}