{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:30:46Z","timestamp":1784334646103,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,12,23]],"date-time":"2010-12-23T00:00:00Z","timestamp":1293062400000},"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":[[2011,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:bold>Aim:\u2003<\/jats:bold> Transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) is involved in renal tubulointerstitial fibrosis. Recently, the ubiquitin proteasome system was shown to participate in the TGF\u2010\u03b2 signalling pathway. The aim of this study was to examine the effects of proteasome inhibitors on TGF\u2010\u03b2\u2010induced transformation of renal fibroblasts and tubular epithelial cells <jats:italic>in vitro<\/jats:italic> and on unilateral ureteral obstruction (UUO) <jats:italic>in vivo<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Methods:\u2003<\/jats:bold> Rat renal fibroblasts NRK\u201049F cells and tubular epithelial cells, NRK\u201052E, were treated with TGF\u2010\u03b2 in the presence or absence of a proteasome inhibitor, MG132 or lactacystin. Rats were subjected to UUO and received MG132 i.p. for 7\u2003days.<\/jats:p><jats:p><jats:bold>Results:\u2003<\/jats:bold> In cultured renal cells, both MG132 and lactacystin inhibited TGF\u2010\u03b2\u2010induced \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA) protein expression according to both western blotting and immunofluorescent study results. MG132 also suppressed TGF\u2010\u03b2\u2010induced mRNA expression of \u03b1\u2010SMA and upregulation of Smad\u2010response element reporter activity. However, MG132 did not inhibit TGF\u2010\u03b2\u2010induced phosphorylation and nuclear translocation of Smad2. In contrast, MG132 increased the protein level of Smad co\u2010repressor SnoN, demonstrating that SnoN is one of the target molecules by which MG132 blocks the TGF\u2010\u03b2 signalling pathway. Although the proteasome inhibitor suppressed TGF\u2010\u03b2\u2010induced transformation of cultured fibroblasts and tubular epithelial cells, MG132 treatment did not ameliorate tubulointerstitial fibrosis in the rat UUO model.<\/jats:p><jats:p><jats:bold>Conclusion:\u2003<\/jats:bold> Proteasome inhibitors attenuate TGF\u2010\u03b2 signalling by blocking Smad signal transduction <jats:italic>in vitro<\/jats:italic>, but do not inhibit renal interstitial fibrosis <jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/j.1440-1797.2010.01367.x","type":"journal-article","created":{"date-parts":[[2010,7,6]],"date-time":"2010-07-06T23:50:28Z","timestamp":1278460228000},"page":"76-86","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Effects of proteasome inhibitors on rat renal fibrosis <i>in vitro<\/i> and <i>in vivo<\/i>"],"prefix":"10.1111","volume":"16","author":[{"given":"TORU","family":"SAKAIRI","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KEIJU","family":"HIROMURA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SATOSHI","family":"TAKAHASHI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HIROKO","family":"HAMATANI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SHIGERU","family":"TAKEUCHI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MAI","family":"TOMIOKA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AKITO","family":"MAESHIMA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TAKASHI","family":"KUROIWA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YOSHIHISA","family":"NOJIMA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,12,23]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V7122495"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00301.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2009.86"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005070757"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007950200009"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-1273rev"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2003.11.003"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006010083"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1361"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2003.07.007"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005101055"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004080681"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002277"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80061-1"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00414.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2009.74"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004670000461"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701991200"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)03163-0"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.5.1431"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00134-9"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/35078562"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200319270"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002717"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.26.15671"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0212736"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.FP0040525"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030288"},{"key":"e_1_2_6_30_2","first-page":"3810","article-title":"Hypoxia promotes fibrogenesis in vivo via HIF\u20101 stimulation of epithelial\u2010to\u2010mesenchymal transition","volume":"117","author":"Higgins DF","year":"2007","journal-title":"J. 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