title: Expression of CCN1 (CYR61) in developing, normal, and diseased human kidney.
abstract: CCN1 (cysteine-rich protein 61; Cyr61) is an extracellular matrix-associated signaling molecule that functions in cell migration, adhesion, and differentiation. We previously reported that CCN1 is induced at podocytes in rat anti-Thy-1 glomerulonephritis, a well-known model of reversible glomerular injury, but its expression and significance in the human kidney remain totally unknown (Sawai K, Mori K, Mukoyama M, Sugawara A, Suganami T, Koshikawa M, Yahata K, Makino H, Nagae T, Fujinaga Y, Yokoi H, Yoshioka T, Yoshimoto A, Tanaka I, Nakao K. J Am Soc Nephrol 14: 1154-1163, 2003). Here we report that, in the human kidney, CCN1 expression was confined to podocytes in normal adult and embryonic glomeruli from the capillary loop stage. Podocyte CCN1 expression was decreased in IgA nephropathy, diabetic nephropathy, and membranous nephropathy, whereas it remained unchanged in minimal change disease and focal segmental glomerulosclerosis. Downregulation of CCN1 was significantly greater in diseased kidneys with severe mesangial expansion. CCN1 protein was also localized in the thick ascending limb of Henle's loop, distal and proximal tubules, and collecting ducts, which was not altered in diseased kidneys. In vitro, recombinant CCN1 protein enhanced endothelial cell adhesion, whereas it prominently inhibited mesangial cell adhesion. CCN1 also completely suppressed mesangial cell migration, suggesting its role as a mesangial-repellent factor. In cultured podocytes, CCN1 markedly induced the expression of cyclin-dependent kinase inhibitor p27(Kip1) as well as synaptopodin in a dose-dependent manner and suppressed podocyte migration. These data indicate that CCN1 is expressed in podocytes, can act on glomerular cells to modulate glomerular remodeling, and is downregulated in diseased kidneys, suggesting that impairment of CCN1 expression in podocytes may contribute to the progression of glomerular disease with mesangial expansion.
authors: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kawahara-cho, Sakyo-ku, Kyoto, Japan.
authors: Kazutomo
authors: K
authors: Sawai
authors: Masashi
authors: M
authors: Mukoyama
authors: Kiyoshi
authors: K
authors: Mori
authors: Masato
authors: M
authors: Kasahara
authors: Masao
authors: M
authors: Koshikawa
authors: Hideki
authors: H
authors: Yokoi
authors: Tetsuro
authors: T
authors: Yoshioka
authors: Yoshihisa
authors: Y
authors: Ogawa
authors: Akira
authors: A
authors: Sugawara
authors: Hiroyuki
authors: H
authors: Nishiyama
authors: Shigehito
authors: S
authors: Yamada
authors: Takashi
authors: T
authors: Kuwahara
authors: Moin A
authors: MA
authors: Saleem
authors: Kohei
authors: K
authors: Shiota
authors: Osamu
authors: O
authors: Ogawa
authors: Mikiya
authors: M
authors: Miyazato
authors: Kenji
authors: K
authors: Kangawa
authors: Kazuwa
authors: K
authors: Nakao
mesh_terms: D000328:Adult; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D055515:Cysteine-Rich Protein 61; D005260:Female; D005922:Glomerulonephritis, IGA / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism* / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology; D007668:Kidney / Q000196:embryology* / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008875:Middle Aged; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27