Angiogenic protein Cyr61 is expressed by podocytes in anti-Thy-1 glomerulonephritis.
Dynamic recovery of glomerular structure occurs after severe glomerular damage in anti-Thy-1 glomerulonephritis (Thy-1 GN), but its mechanism remains to be investigated. To identify candidate genes possibly involved in glomerular reconstruction, screening was performed for genes that are specifically expressed by podocytes and are upregulated in glomeruli of Thy-1 GN. Among them, cysteine-rich protein 61 (Cyr61 or CCN1), a soluble angiogenic protein belonging to the CCN family, was identified. By Northern blot analysis, Cyr61 mRNA was markedly upregulated in glomeruli of Thy-1 GN from day 3 through day 7, when mesangial cell migration was most prominent. By in situ hybridization and immunohistochemistry, Cyr61 mRNA and protein were expressed by proximal straight tubules and afferent and efferent arterioles in normal rat kidneys and were intensely upregulated at podocytes in Thy-1 GN. Platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta1 (TGF-beta1), of which the gene expression in the glomeruli of Thy-1 GN was upregulated in similar time course as Cyr61, induced Cyr61 mRNA expression in cultured podocytes. Furthermore, supernatant of Cyr61-overexpressing cells inhibited PDGF-induced mesangial cell migration. In conclusion, it is shown that Cyr61 is strongly upregulated at podocytes in Thy-1 GN possibly by PDGF and TGF-beta. Cyr61 may be involved in glomerular remodeling as a factor secreted from podocytes to inhibit mesangial cell migration.
Sawai
Kazutomo
K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Mori
Kiyoshi
K
Mukoyama
Masashi
M
Sugawara
Akira
A
Suganami
Takayoshi
T
Koshikawa
Masao
M
Yahata
Kensei
K
Makino
Hisashi
H
Nagae
Tetsuya
T
Fujinaga
Yuriko
Y
Yokoi
Hideki
H
Yoshioka
Tetsuro
T
Yoshimoto
Akihiro
A
Tanaka
Issei
I
Nakao
Kazuwa
K
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000077214:Becaplermin; D002455:Cell Division / Q000502:physiology; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000502:physiology; D055515:Cysteine-Rich Protein 61; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D015723:Gene Library; D005920:Glomerular Mesangium / Q000166:cytology*; D005921:Glomerulonephritis / Q000473:pathology / Q000503:physiopathology*; D017874:Immediate-Early Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D018800:Thy-1 Antigens / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation
D043925:Angiogenesis Inducing Agents; D000911:Antibodies, Monoclonal; C491850:CCN1 protein, mouse; C501849:CCN1 protein, rat; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; D018800:Thy-1 Antigens; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000077214:Becaplermin