Connective Tissue Growth Factor: What's in a Name?

Moussad, Essam El-Din A.; Brigstock, David R.

doi:10.1006/mgme.2000.3059

Cited by 449 publications

(397 citation statements)

References 87 publications

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“…CTGF is a cytokine that has been widely studied in its role in connective tissue fibrosis but it is expressed in far more cell types than connective tissue and it has been shown to play roles in a wide variety of cell processes (Moussad and Brigstock 2000). The present study shows that it is normally present in type IV fibrocytes, root cells, and upper turn Deiters cells.…”

Section: Implications Of the Findingsmentioning

confidence: 47%

“…It has been found to also play roles in diverse autocrine or paracrine actions upon other cell types, including vascular endothelial and smooth muscle cells, epithelial cells, neurons, glia, and bone cells (Moussad and Brigstock 2000;Brigstock 2003). Its function in the cochlea remains to be demonstrated, but the present finding of a CTGF receptor (LRP1) in a number of cochlear cells raises the possibility that it plays a paracrine role with LRP1-immunopositive cells.…”

Section: Implications Of the Findingsmentioning

confidence: 71%

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Immunocytochemical Traits of Type IV Fibrocytes and Their Possible Relations to Cochlear Function and Pathology

Adams

2009

JARO

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One of the more consistent and least understood changes in the aging human cochlea is the progressive loss of fibrocytes within the spiral ligament. This report presents an animal model for type IV fibrocyte loss, along with immunocytochemical evidence that noise-induced loss of these cells may account for previously unexplained hearing losses. The remarkably low threshold for noise-induced loss of type IV fibrocytes, approximately 24 dB less than the threshold for adjacent hair cell destruction, may account for the prevalence of missing fibrocytes in humans. In mice, changes in the spectrum of traumatizing noise had little effect upon the site of loss of the fibrocytes, suggesting that the primary site of damage that induced the loss was the basal-most cochlear turn, a site expected to be damaged by all three noise bands. Type IV fibrocytes were found to immunostain for connective tissue growth factor (CTGF) and for transforming growth factor beta receptor 3, a receptor that is known to activate CTGF expression. Type IV fibrocytes lack immunostaining for adenosine triphosphatase and connexins that are key players in potassium ion uptake and transmission, which suggests that they play little, if any, role in potassium recycling from perilymphatic space to the endolymphatic space. Consequently, their loss probably does not directly reduce this process. Immunostaining for a receptor for CTGF, low-density-lipoprotein-related protein 1, indicated that CTGF acts as an autocrine and a paracrine agent within the cochlea. The lack of CTGF paracrine effects following noise-induced loss of type IV fibrocytes may account for previously unexplained hearing losses.

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Section: Implications Of the Findingsmentioning

confidence: 47%

Section: Implications Of the Findingsmentioning

confidence: 71%

Immunocytochemical Traits of Type IV Fibrocytes and Their Possible Relations to Cochlear Function and Pathology

Adams

2009

JARO

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“…32,7 The important finding in our study was that, in dTGR, Ang II induces myocardial and renal CTGF mRNA and protein expression via AT 1 receptor. The effect appeared to be ageand blood pressure-dependent.…”

Section: Discussionmentioning

confidence: 59%

Angiotensin II Induces Connective Tissue Growth Factor Gene Expression via Calcineurin-Dependent Pathways

Finckenberg

Inkinen

Ahonen

et al. 2003

The American Journal of Pathology

102

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Connective tissue growth factor (CTGF) is a polypeptide implicated in the extracellular matrix synthesis.Previous studies have provided evidence that angiotensin II (Ang II) promotes collagen synthesis and regulates collagen degradation. We investigated whether or not CTGF mediates the profibrotic effects of Ang II in the heart and kidneys and the role of calcineurin-dependent pathways in CTGF gene regulation. In transgenic rats harboring human renin and angiotensinogen genes, Ang II induced an age-dependent increase in myocardial CTGF expression, which was 3.5-fold greater compared to normotensive Sprague Dawley (SD) rats. CTGF overexpression correlated closely with the Ang II-induced rise in blood pressure. CTGF mRNA and protein were located predominantly in areas with leukocyte infiltration, myocardial, and vascular lesions and co-localized with TGF␤ 1 , collagen I, and collagen III mRNA expressions. Ang II induced CTGF mRNA and protein to a lesser extent in the kidneys, predominantly in glomeruli, arterioles, and in the interstitium with ample inflammation. However, no expression was found in the right ventricle or pulmonary arteries. Blockade of calcineurin activity by cyclosporine A completely normalized Ang II-induced CTGF overexpression in heart and kidney, suppressed the inflammatory response, and mitigated Ang II-induced cell proliferation and apoptosis. In contrast, blockade of mTOR (target of rapamycin) pathway by everolimus, further increased the expression of CTGF even though everolimus ameliorated cell proliferation and T-cellmediated inflammation. Our findings provide evidence that CTGF mediates Ang II-induced fibrosis in the heart and kidneys via blood pressure and cal-

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“…A recent gene profiling analysis [Kang et al, 2003] comparing non-metastatic breast cancer cells and their metastatic derivatives identified CTGF and FGF5 as among only a handful of metastatic signature genes. CTGF is known to have pro-angiogenic as well as profibrogenic properties [Moussad and Brigstock, 2000], and FGF5 was originally isolated also as a factor that sustained NIH3T3 fibroblast growth in the absence of serum. Furthermore, FGF5 knockout mice showed abnormal hair growth [Hebert et al, 1994], again implicating this growth factor as a stromal regulator.…”

Section: Epithelial-stromal Cell Interactions and The Tumor Micro-envmentioning

confidence: 99%

“…1). CTGF is induced by TGFβ [Moussad and Brigstock, 2000], emanating either from fibroblasts or immune cells within the stroma, although whether this functional correlation is mediated by Ets factors remains to be elucidated. FGF5-induced signaling has not been specifically linked to Ets factors; however, this model is likely as FGF receptor-mediated Ras-MAPK signaling is the prototype Ets modulator.…”

Section: Epithelial-stromal Cell Interactions and The Tumor Micro-envmentioning

confidence: 99%

Ets proteins in biological control and cancer

Hsu

Trojanowska

Watson

2004

J of Cellular Biochemistry

257

202

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The Ets family consists of a large number of evolutionarily conserved transcription factors, many of which have been implicated in tumor progression. Extensive studies on this family of proteins have focused so far mainly on the biochemical properties and cellular functions of individual factors. Since most of the Ets factors can bind to the core consensus DNA sequence GGAA/T in vitro, it has been a challenge to differentiate redundant from specific functions of various Ets proteins in vivo. Recent findings, however, suggest that such apparent redundancy may in fact be a central component of a network of differentially regulated specific Ets factors, resulting in distinct biological and pathological consequences. The programmed "Ets conversion" appears to play a critical role during tumor progression, especially in control of cellular changes during epithelial-mesenchymal transition and metastasis. Coordination of multiple Ets gene functions also mediates interactions between tumor and stromal cells. As such, these new insights may provide a novel view of the Ets gene family as well as a focal point for studying the complex biological control involved in tumor progression. KeywordsEts; transcriptional regulation; ECM; cancer; invasion; metastasis; EMT; epithelium; stroma The Ets family of proteins consists of a large number of evolutionarily conserved transcription factors. There are 25 human and 26 murine Ets family members. Ets factors control specific genes that perform critical roles in diverse processes, including cell proliferation, apoptosis, differentiation, lymphoid cell development, angiogenesis, and invasiveness [Sementchenko and Watson, 2000]. To date, studies in the field have largely focused on individual Ets factors and have indeed yielded valuable, albeit fragmented, information. Recent findings, on the other hand, have suggested that several Ets factors may participate in a coordinated program that modulates cell migration and invasiveness, thus affecting tumor progression toward metastasis. In this review, we will examine the recent progress in Ets biology and provide a forum for discussion on a systemic view of Ets functions. Detailed descriptions of Ets proteins and their functions have been provided in several recent reviews [Watson and Seth, 2000;Watson et al., 2001;Dittmer, 2003;Oikawa and Yamada, 2003].Cancer results from a multi-step series of genetic changes that lead to essential alterations in cell physiology such as loss of growth controls and normal apoptotic response as well as sustained angiogenesis, invasion, and metastasis [Hanahan and Weinberg, 2000]. While it is known that most human tumors are derived from epithelial cells that have undergone multiple genetic alterations [Hanahan and Weinberg, 2000], it is also becoming clear that the alterations

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Connective Tissue Growth Factor: What's in a Name?

Cited by 449 publications

References 87 publications

Immunocytochemical Traits of Type IV Fibrocytes and Their Possible Relations to Cochlear Function and Pathology

Immunocytochemical Traits of Type IV Fibrocytes and Their Possible Relations to Cochlear Function and Pathology

Angiotensin II Induces Connective Tissue Growth Factor Gene Expression via Calcineurin-Dependent Pathways

Ets proteins in biological control and cancer

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