{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:12:04Z","timestamp":1790475124674,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,10,24]],"date-time":"2016-10-24T00:00:00Z","timestamp":1477267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>\n                    The purpose of our study was to evaluate how hyperglycemia (HG)influences Lys63 protein ubiquitination and its involvement in tubular damage and fibrosis in diabetic nephropathy (DN). Gene and protein expression of UBE2v1, a ubiquitin\u2010conjugating E2\u2010enzyme variant that mediates Lys63\u2010linked ubiquitination, and Lys63\u2010 ubiquitinated proteins increased in HK2 tubular cells under HG. Matrix\u2010assisted laser desorption\/ionization\u2013time of flight\/tandemmass spectrometry identified 30 Lys63\u2010ubiquitinated proteins, mainly involved in cellular organization, such as \u03b2\u2010actin, whose Lys63 ubiquitination increased under HG, leading to cytoskeleton disorganization. This effect was reversed by the inhibitor of the Ubc13\/UBE2v1 complexNSC697923. Western blot analysis confirmed that UBE2v1 silencing in HK2 under HG, restored Lys63\u2010\u03b2\u2010actin ubiquitination levels to the basal condition. Immuno histochemistry on patients with type 2 diabetic (T2D) revealed an increase in UBE2v1\u2010 and Lys63\u2010ubiquitinated proteins, particularly in kidneys of patients with DN compared with control kidneys and other nondiabetic renal diseases, such as membranous nephropathy. Increased Lys63 ubiquitination both\n                    <jats:italic>in vivo<\/jats:italic>\n                    in patients with DN and\n                    <jats:italic>in vitro<\/jats:italic>\n                    , correlated with \u03b1\u2010SMA expression, whereas UBE2v1 silencing reduced HG\u2010induced \u03b1\u2010SMA protein levels, returning them to basal expression. In conclusion, UBE2v1\u2010 and Lys63\u2010ubiquitinated proteins increase\n                    <jats:italic>in vitro<\/jats:italic>\n                    under HG, as well as\n                    <jats:italic>in vivo<\/jats:italic>\n                    in T2D, is augmented in patients with DN, and may affect cytoskeleton organization and influence epithelial\u2010to\u2010mesenchymal transition. This process may drive the progression of tubular damage and interstitial fibrosis in patients with DN.\u2014Pontrelli, P., Conserva, F., Papale, M., Oranger, A., Barozzino, M., Vocino, G., Rochetti, M. T., Gigante, M., Castellano, G., Rossini, M., Simone, S., Laviola, L., Giorgino, F., Grandaliano, G., DiPaolo, S., Gesualdo, L. Lysine 63 ubiquitination is involved in the progression of tubular damage in diabetic nephropathy. FASEB J. 31, 308\u2013319 (2017)\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201600382rr","type":"journal-article","created":{"date-parts":[[2016,10,24]],"date-time":"2016-10-24T23:19:21Z","timestamp":1477351161000},"page":"308-319","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Lysine 63 ubiquitination is involved in the progression of tubular damage in diabetic nephropathy"],"prefix":"10.1096","volume":"31","author":[{"given":"Paola","family":"Pontrelli","sequence":"first","affiliation":[{"name":"Division of Nephrology Dialysis, Transplantation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Conserva","sequence":"additional","affiliation":[{"name":"Division of Nephrology Dialysis, Transplantation"},{"name":"Department of Cardiology and Cardiac Rehabilitation Scientific Clinical Institute of Maugeri  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Papale","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medical and Surgical Sciences University of Foggia  Foggia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarita","family":"Oranger","sequence":"additional","affiliation":[{"name":"Division of Nephrology Dialysis, Transplantation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariagrazia","family":"Barozzino","sequence":"additional","affiliation":[{"name":"Division of Nephrology Dialysis, Transplantation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Vocino","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medical and Surgical Sciences University of Foggia  Foggia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teres.","family":"Rocchetti","sequence":"additional","affiliation":[{"name":"Division of Nephrology Dialysis, Transplantation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Gigante","sequence":"additional","affiliation":[{"name":"Division of Nephrology Dialysis, Transplantation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Castellano","sequence":"additional","affiliation":[{"name":"Division of Nephrology Dialysis, Transplantation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Rossini","sequence":"additional","affiliation":[{"name":"Division of Nephrology Dialysis, Transplantation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Simone","sequence":"additional","affiliation":[{"name":"Division of Nephrology Dialysis, Transplantation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Laviola","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Emergency and Organ Transplantation University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Giorgino","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Emergency and Organ Transplantation University of Bari  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Grandaliano","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medical and Surgical Sciences University of Foggia  Foggia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"di Paolo","sequence":"additional","affiliation":[{"name":"Nephrology Unit Dimiccoli Hospital  Barletta Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loreto","family":"Gesualdo","sequence":"additional","affiliation":[{"name":"Division of Nephrology Dialysis, Transplantation"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,10,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.diabres.2008.09.042","article-title":"Diabetic nephropathy: important pathophysiologic mechanisms","author":"Soldatos G.","year":"2008","journal-title":"Diabetes Res. 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