Uptake and intracellular transport of the connective tissue growth factor: a potential mode of action

Wahab, Nadia Abdel; Brinkman, Heike; Mason, Roger M.

doi:10.1042/0264-6021:3590089

Cited by 62 publications

(55 citation statements)

References 53 publications

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“…In normal kidney, the main site of Cyr61 expression was proximal straight tubules. On the contrary, we and others have shown that neither CTGF gene (19,38) nor protein (31,39,40) are expressed in normal proximal tubules. In glomeruli of Thy-1 GN, Cyr61 protein expression was predominantly induced in podocytes, whereas CTGF gene expression is broadly upregulated in podocytes, glomerular parietal epithelial cells, mesangial cells, and periglomerular myofibroblasts (39).…”

Section: Discussionmentioning

confidence: 97%

Angiogenic Protein Cyr61 is Expressed by Podocytes in Anti-Thy-1 Glomerulonephritis

Sawai¹,

Mori²,

Mukoyama³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. 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-␤1 (TGF-␤1), 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-␤. Cyr61 may be involved in glomerular remodeling as a factor secreted from podocytes to inhibit mesangial cell migration.

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Section: Discussionmentioning

confidence: 97%

Angiogenic Protein Cyr61 is Expressed by Podocytes in Anti-Thy-1 Glomerulonephritis

Sawai¹,

Mori²,

Mukoyama³

et al. 2003

Journal of the American Society of Nephrology

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“…CCN2 and CCN3 proteins have been observed in the nucleus in some cells (Wahab et al 2001;Planque et al 2006). Nuclear localization of CCN2 and CCN5 has also been observed in cultured rat aortic, uterine, and tracheal smooth muscle cells using immunofluorescent staining and confocal microscopy methods (manuscript in preparation).…”

Section: Discussionmentioning

confidence: 98%

CCN5 Expression in mammals. II. Adult rodent tissues

Gray

Malmquist

Sullivan

et al. 2007

J. Cell Commun. Signal.

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CCN5 is a secreted heparin-and estrogenregulated matricellular protein that inhibits vertebrate smooth muscle cell proliferation and motility. CCN5 is expressed throughout murine embryonic development in most organs and tissues. However, after embryonic development is complete, we hypothesized that CCN5 distribution would be largely restricted to small set of tissues, including smooth muscle cells of the arteries, uterus, airway, and digestive tract. Because CCN5 inhibits proliferation of smooth muscle cells in vitro, it might function to prevent excessive growth in vivo. In contrast, another member of the CCN family, CCN2, promotes smooth muscle cell proliferation in vitro, and thus it was expected that its expression levels would be low in uninjured normal adult tissues. Frozen sections from adult tissues and organs were analyzed immunohistochemically using anti-CCN5 and anti-CCN2 antibodies. Both proteins were detected in arteries, the uterus, bronchioles, and the digestive tract as expected, and also in many other tissues including the pancreas, spleen, liver, skeletal muscle, ovary, testis, thymus, brain, olfactory epithelium, and kidney. CCN5 and CCN2 protein was found in smooth muscle, endothelial cells, epithelial cells, skeletal muscle, cells of the nervous system, and numerous other cell types. In many cells, both CCN5 and CCN2 was present in the nucleus. Rather than having opposite patterns of localization, CCN5 and CCN2 often had similar sites of expression. The wide distribution of both CCN5 and CCN2 suggests that both proteins have additional biological functions beyond those previously identified in specific cellular and pathological models.

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“…Nuclear localization was particularly prominent in the cells of the spinal cord and adrenal gland. Both CCN2 and CCN3 have been detected in the nucleus and are likely to help regulate transcription (Gellhaus et al 2004;Perbal 1999;Wahab et al 2001). Amino-truncated but not full length CCN3 has been detected in cell nuclei, and CCN3-Gal4 fusion proteins can reduce transcription of reporter genes with Gal4 binding sites (Perbal 1999).…”

Section: Discussionmentioning

confidence: 99%

CCN5 expression in mammals

Jones

Gray

Oliveira

et al. 2007

J. Cell Commun. Signal.

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The six proteins of the CCN family have important roles in development, angiogenesis, cell motility, proliferation, and other fundamental cell processes. To date, CCN5 distribution in developing rodents and humans has not been mapped comprehensively. CCN5 strongly inhibits adult smooth muscle cell proliferation and motility. Its antiproliferative action predicts that CCN5 would not be present in developing tissues until the proliferation phase of tissue morphogenesis is complete. However, estrogen induces CCN5 expression in epithelial and smooth muscle cells, suggesting that CCN5 might be widely expressed in embryonic tissues exposed to high levels of estrogen.9-16 day murine embryos and fetuses and 3-7 month human fetal tissues were analyzed by immunohistochemistry. CCN5 was detected in nearly all developing tissues. CCN5 protein expression was initially present in most tissues, and at later times in development tissue-specific expression differences were observed. CCN5 expression was particularly strong in vascular tissues, cardiac muscle, bronchioles, myotendinous junctions, and intestinal smooth muscle and epithelium. CCN5 expression was initially absent in bone cartilaginous forms but was increasingly expressed during bone endochondral ossification. Widespread CCN5 mRNA expression was detected in GD14.5 mice. Although CCN2 and CCN5 protein expression patterns in some adult pathologic conditions are inversely expressed, this expression pattern was not found in developing mouse and human tissues. The widespread expression pattern of CCN5 in most embryonic and fetal tissues suggests a diverse range of functions for CCN5.

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Uptake and intracellular transport of the connective tissue growth factor: a potential mode of action

Cited by 62 publications

References 53 publications

Angiogenic Protein Cyr61 is Expressed by Podocytes in Anti-Thy-1 Glomerulonephritis

Angiogenic Protein Cyr61 is Expressed by Podocytes in Anti-Thy-1 Glomerulonephritis

CCN5 Expression in mammals. II. Adult rodent tissues

CCN5 expression in mammals

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