{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:14:17Z","timestamp":1790892857382,"version":"4.1.0"},"reference-count":92,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2003,7,1]],"date-time":"2003-07-01T00:00:00Z","timestamp":1057017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2003,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The alterations in the microvascular system of diabetes mellitus patients are responsible for the most devastating complications of this widespread disease. In the kidney, the microangiopathy leads to thickening of the glomerular capillary basement membrane but also to the expansion of the mesangial matrix and thickening of the tubular basement membrane. Several mechanisms are implicated in the pathogenesis of diabetic renal microangiopathy. These include increased synthesis of type IV collagen following hyperglycaemia\u2010induced alteration of the pattern of podocyte\u2013integrin expression, decreased expression of matrix metalloproteinases (MMP\u20102 and 3), and increased expression of tissue inhibitor of metalloproteinase (TIMP). An altered morphology of podocytes accompanies these basement membrane alterations. Other factors which may contribute to renal matrix accumulation include vascular endothelial growth factor (VEGF), since treatment with anti\u2010VEGF antibodies attenuates glomerular basement membrane thickening, platelet\u2010derived growth factor (PDGF) (B chain) and its receptor, which appear to be highly expressed in mesangial and visceral epithelial cells and might play a role in the development of diabetic nephropathy. Also oxygen radicals\/oxidative stress may play a role in matrix accumulation in diabetic nephropathy as aminoguanidine, an inhibitor of the formation of advanced glycation end\u2010products but with antioxidant properties, attenuates diabetic nephropathy. Retinal diabetic microangiopathy follows much the same principles, be it that microvascular proliferation is a distinctive element in the retina. Nephropathy and retinopathy occur frequently but not always together, indicating that in their multifactorial pathogenesis much remains to be clarified. Copyright \u00a9 2003 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.1439","type":"journal-article","created":{"date-parts":[[2003,7,2]],"date-time":"2003-07-02T06:02:59Z","timestamp":1057125779000},"page":"537-546","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":207,"title":["Microvascular basement membranes in diabetes mellitus"],"prefix":"10.1002","volume":"200","author":[{"given":"Effie C","family":"Tsilibary","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,7]]},"reference":[{"issue":"2","key":"e_1_2_7_2_2","first-page":"S424","article-title":"Pathogenesis of diabetic nephropathy","volume":"109","author":"Raptis AE","year":"2001","journal-title":"Diabetes"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.9.1399"},{"key":"e_1_2_7_4_2","first-page":"8","article-title":"Structural involvement in type 1 and type 2 diabetic nephropathy","volume":"4","author":"Della Vestra M","year":"2000","journal-title":"Diabetes Metab Suppl"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00422369"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1076\/apab.109.3.241.11592"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.10.3083"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00266.2002"},{"key":"e_1_2_7_9_2","first-page":"650","article-title":"Integrin\u2010mediated interactions between primary\/T\u2010sv40 immortalized human glomerular epithelial cells and type IV collagen","volume":"74","author":"Krishnamurti U","year":"1996","journal-title":"Lab Invest"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050637"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(00)00815-8"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.2001.29228"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(96)04215-2"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990331)81:1<90::AID-IJC16>3.0.CO;2-K"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.146.6.1375"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.16.2909"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20000701)87:1<12::AID-IJC3>3.0.CO;2-A"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1159\/000147926"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.LAB.0000022224.86237.31"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1159\/000064110"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1016398200087"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1053\/meta.2001.28074"},{"key":"e_1_2_7_23_2","first-page":"290","article-title":"Urinary glycosaminoglycan and proteoglycan excretion in normoalbuminuric patients with type 1 diabetes mellitus","volume":"15","author":"De Muro P","year":"2002","journal-title":"J Nephrol"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00858.x"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1159\/000052614"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050989"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.4.522"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02708-0"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64802-X"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02084-3"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.2003.50011"},{"key":"e_1_2_7_32_2","first-page":"F571","article-title":"High glucose increases diacylglycerol mass and activates protein kinase C in mesangial cell cultures","volume":"261","author":"Ayo SH","year":"1991","journal-title":"Am J Physiol"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8227(02)00194-8"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.44.27966"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf535"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.12.3505"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00181.2002"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051567"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.3109\/15419069609010765"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8529(05)70324-8"},{"key":"e_1_2_7_41_2","first-page":"1087","article-title":"Advanced glycosylation end products, protein kinase C and renal alterations in diabetic rats","volume":"113","author":"Rong J","year":"2000","journal-title":"Chin Med J (Engl)"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.2002.00932.x"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V1191656"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1463-1326.2002.00182.x"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.7.1114"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/12.4.643"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050730"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00478.x"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.10.3090"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8227(99)00144-8"},{"key":"e_1_2_7_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03402014"},{"key":"e_1_2_7_52_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004670200004"},{"key":"e_1_2_7_53_2","first-page":"247","article-title":"Diabetic nephropathy: the central role of renal proximal tubular cells in tubulointerstitial injury","volume":"17","author":"Philips AO","year":"2002","journal-title":"Histol Histopathol"},{"key":"e_1_2_7_54_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.12.3532"},{"key":"e_1_2_7_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61150-9"},{"key":"e_1_2_7_56_2","doi-asserted-by":"publisher","DOI":"10.3109\/15419069509081286"},{"key":"e_1_2_7_57_2","first-page":"S51","article-title":"Role of mesangial expansion in the pathogenesis of diabetic nephropathy","volume":"4","author":"Dalla Vestra M","year":"2001","journal-title":"J Nephrol"},{"key":"e_1_2_7_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(12)80971-1"},{"key":"e_1_2_7_59_2","doi-asserted-by":"publisher","DOI":"10.1159\/000013495"},{"key":"e_1_2_7_60_2","first-page":"2003","article-title":"Mesangial cell proliferation inhibitors for the treatment of proliferative glomerular disease","volume":"23","author":"Kugori Y","journal-title":"Med Res Rev"},{"key":"e_1_2_7_61_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1998.274.6.F1045"},{"key":"e_1_2_7_62_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0089fje"},{"key":"e_1_2_7_63_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199807093390202"},{"key":"e_1_2_7_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.455"},{"key":"e_1_2_7_65_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.2.349"},{"key":"e_1_2_7_66_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.43.3.441"},{"key":"e_1_2_7_67_2","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.1998.39.5.453"},{"key":"e_1_2_7_68_2","doi-asserted-by":"publisher","DOI":"10.1076\/0271-3683(200007)2111-ZFT581"},{"key":"e_1_2_7_69_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1750233"},{"key":"e_1_2_7_70_2","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.18.6.490.5267"},{"key":"e_1_2_7_71_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.4.662"},{"key":"e_1_2_7_72_2","doi-asserted-by":"publisher","DOI":"10.1177\/44.12.8985139"},{"key":"e_1_2_7_73_2","first-page":"2758","article-title":"Effects of tenascin\u2010C on normal and diabetic retinal endothelial cells in culture","volume":"43","author":"Castellon R","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_7_74_2","first-page":"809","article-title":"Human diabetic neovascular membranes contain high levels of urokinase and metalloproteinase enzymes","volume":"40","author":"Das A","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_7_75_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-15279"},{"key":"e_1_2_7_76_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-001-0727-z"},{"key":"e_1_2_7_77_2","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.22.3.190.5519"},{"key":"e_1_2_7_78_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-001-0761-x"},{"key":"e_1_2_7_79_2","first-page":"2358","article-title":"Altered proliferation of retinal microvascular cells on glycated matrix","volume":"36","author":"Kalfa TA","year":"1995","journal-title":"Invest Ophthalm Vis Sci"},{"key":"e_1_2_7_80_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051221"},{"key":"e_1_2_7_81_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-002-0575-7"},{"key":"e_1_2_7_82_2","first-page":"325","article-title":"Modification of vitronectin by advanced glycation alters functional properties in vitro and in the diabetic retina","volume":"75","author":"Hammes HP","year":"1996","journal-title":"Lab Invest"},{"key":"e_1_2_7_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8727(97)00051-2"},{"key":"e_1_2_7_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02584-6"},{"key":"e_1_2_7_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8227(01)00299-6"},{"key":"e_1_2_7_86_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.3.401"},{"key":"e_1_2_7_87_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.10.3107"},{"key":"e_1_2_7_88_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105336200"},{"key":"e_1_2_7_89_2","doi-asserted-by":"publisher","DOI":"10.1007\/s109-1998-8101-y"},{"key":"e_1_2_7_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8727(01)00229-X"},{"key":"e_1_2_7_91_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb02108.x"},{"key":"e_1_2_7_92_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.07705.x"},{"key":"e_1_2_7_93_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V1171236"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.1439","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.1439","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.1439","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T11:28:02Z","timestamp":1761046082000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.1439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,7]]},"references-count":92,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2003,7]]}},"alternative-id":["10.1002\/path.1439"],"URL":"https:\/\/doi.org\/10.1002\/path.1439","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,7]]},"assertion":[{"value":"2003-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}