title: Upregulation of α3β1-Integrin in Podocytes in Early-Stage Diabetic Nephropathy.
abstract: Background. Podocyte injury plays an important role in the onset and progression of diabetic nephropathy (DN). Downregulation of α3β1-integrin expression in podocytes is thought to be associated with podocyte detachment from the glomerular basement membrane, although the mechanisms remain obscure. To determine the mechanism of podocyte detachment, we analyzed the expression levels of α3β1-integrin in podocytes in early and advanced stages of DN. Methods. Surgical specimens from DN patients were examined by in situ hybridization, and the expression levels of α3- and β1-integrin subunits in glomeruli of early (n = 6) and advanced (n = 8) stages were compared with those of normal glomeruli (n = 5). Heat-sensitive mouse podocytes (HSMP) were cultured with TGF-β1 to reproduce the microenvironment of glomeruli of DN, and the expression levels of integrin subunits and the properties of migration and attachment were examined. Results. Podocytes of early-stage DN showed upregulation of α3- and β1-integrin expression while those of advanced stage showed downregulation. Real-time PCR indicated a tendency for upregulation of α3- and β1-integrin in HSMP cultured with TGF-β1. TGF-β1-stimulated HSMP also showed enhanced in vitro migration and attachment on collagen substrate. Conclusions. The results suggested that podocyte detachment during early stage of DN is mediated through upregulation of α3β1-integrin.
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Kaichiro
authors.initials: K
authors.lastname: Sawada
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Masao
authors.identifier: 0000-0003-4142-1218
authors.initials: M
authors.lastname: Toyoda
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kaneyama
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Shiraiwa
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Moriya
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Han
authors.initials: H
authors.lastname: Miyatake
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Eitaro
authors.initials: E
authors.lastname: Tanaka
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyauchi
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Moritsugu
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Wada
authors.affiliation: Division of Nephrology, Endocrinology and Metabolism, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
mesh_terms: D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D039201:Integrin alpha3beta1; D053773:Transforming Growth Factor beta1