Connective Tissue Growth Factor and Regulation of the Mesangial Cell Cycle

Abdel-Wahab, Nadia; Weston, Benjamin S.; Roberts, Terry; Mason, Roger M.

doi:10.1097/01.asn.0000031828.58276.02

Cited by 108 publications

(54 citation statements)

References 73 publications

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“…This is consistent with the fact that established diabetic nephropathy is associated with mesangial cell hypertrophy rather than with cell proliferation (25). CTGF stimulates mesangial cells to enter the cell cycle and arrests progression at the G1 phase (24). This was achieved through the induction of the negative regulators of the cell cycle CDKI p15 INK4 , p21…”

Section: Connective Tissue Growth Factorsupporting

confidence: 70%

“…CTGF has also been reported to have a direct role in modulation of the mesangial cell cycle (24). This is consistent with the fact that established diabetic nephropathy is associated with mesangial cell hypertrophy rather than with cell proliferation (25).…”

Section: Connective Tissue Growth Factorsupporting

confidence: 68%

“…Cip1 , and p27 Kip1 , which subsequently bound to and inactivated cyclin D/CDK4/6 and cyclin E/CDK2 kinase complexes (24). Cells arrested in the G1 phase showed increased size and exhibited enhanced RNA and protein synthesis, resulting in cellular hypertrophy (24).…”

Section: Connective Tissue Growth Factormentioning

confidence: 99%

“…Cells arrested in the G1 phase showed increased size and exhibited enhanced RNA and protein synthesis, resulting in cellular hypertrophy (24). Furthermore, the investigators provided evidence that TGF-␤ had a positive regulatory effect on expression of all three CDKI and that this effect was mediated through CTGF (24).…”

Section: Connective Tissue Growth Factormentioning

confidence: 99%

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Transcriptome Profiling and the Pathogenesis of Diabetic Complications

Connolly

Sadlier

Kieran

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Diabetes is an escalating problem worldwide and a major cause of vascular disease, renal failure, and blindness, among other complications. The cellular mediators of high glucose-induced injury include activation of protein kinase C, accumulation of cell sorbitol from increased flux through the aldose reductase pathway, and generation of advanced glycosylation end products and reactive oxygen species, among others. Current strategies for preventing and slowing the progression of the macrovascular and microvascular complications of diabetes include optimization of glycemic control and BP, angiotensin-converting enzyme inhibitors and angiotensin II blockers, and HMG CoA reductase inhibitors. However, there is an urgent need to develop new therapeutic strategies, as these interventions, although they may slow, rarely halt the progression of diabetic complications. Central to this process is the elucidation of the molecular events that drive this complex disease and that are potential therapeutic targets. This review discusses the promise offered in this regard by global monitoring of cellular or tissue mRNA expression (so-called transcriptomics) and illustrates the potential of this approach by focusing on recent studies on the pathogenesis of diabetic nephropathy.

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Section: Connective Tissue Growth Factorsupporting

confidence: 70%

Section: Connective Tissue Growth Factorsupporting

confidence: 68%

Section: Connective Tissue Growth Factormentioning

confidence: 99%

Section: Connective Tissue Growth Factormentioning

confidence: 99%

See 2 more Smart Citations

Transcriptome Profiling and the Pathogenesis of Diabetic Complications

Connolly

Sadlier

Kieran

et al. 2003

Journal of the American Society of Nephrology

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“…Cell proliferation and hypertrophy were measured by the previous method (Wahab et al, 2002). At the end of stimulation period, GMCs were washed three times with ice-cold PBS (pH 7.4) and collected using 0.25% trypsin and 0.5% EDTA, followed by centrifuging at 1,000 g for 5 min.…”

Section: Cell Proliferation and Hypertrophy Assaymentioning

confidence: 99%

TGF-β1-induced PINCH-1-ILK-α-parvin complex formation regulates mesangial cell proliferation and hypertrophy

Kim

Kim²,

Lee³

et al. 2007

Exp Mol Med

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TGF-β1-induced glomerular mesangial cell (GMC) injury is a prominent characteristic of renal pathology in several kidney diseases, and a ternary protein complex consisting of PINCH-1, integrin-linked kinase (ILK) and α-parvin plays a pivotal role in the regulation of cell behavior such as cell proliferation and hypertrophy. We report here that PINCH-1-ILK-α-parvin (PIP) complex regulates the TGF-β1-induced cell proliferation and hypertrophy in cultured rat GMCs. When GMCs were treated with TGF-β1 for 1, 2 and 3 days, the PIP complex formation was up-regulated after 1 day, but it was down-regulated on day 2. Cell numbers were significantly elevated on day 2, but dramatically decreased on day 3. In contrast, a significant increase in cellular protein contents was observed 3 days after TGF-β1-treatment. TGF-β1 induced early increase of caspase-3 activity. In GMCs incubated with TGF-β1 for 2 days, cytosolic expression of p27 Kip1 was dramatically reduced, but its nuclear expression was remarkably elevated. A significantly decreased expression of phospho-Akt (Ser 473) was observed in the cells treated with TGF-β1 for 1 day. TGF-β1 induced early increase of phospho-p27 Kip1 (Thr 157) expression with subsequent decrease, and similar responses to TGF-β1 were observed in the p38 phosphorylation (Thr 180/Thr 182). Taken together, TGF-β1 differently regulates the PIP complex formation of GMCs in an incubation period-dependant fashion. The TGF-β1-induced up-and down-regulation of the PIP complex formation likely contributes to the pleiotropic effects of TGF-β1 on mesangial cell proliferation and hypertrophy through cellular localization of p27Kip1 and alteration of Akt and p38 phosphorylation. TGF-β1-induced alteration of the PIP complex formation may be importantly implicated in the development and progression of glomerular failure shown in several kidney diseases.

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Pathogenesis of Diabetic Microvascular Complications

Rask‐Madsen

King

2004

International Textbook of Diabetes Mellitus

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Complications of diabetes have been the leading cause of mortality and morbidity in both type 1 and type 2 diabetes. Based on the sites of functional and pathological changes, these complications have been characterized as cardiomyopathy, macrovasculopathy, and microvasculopathy. Multiple clinical studies have shown that glycemic control is by far the most effective approach in the prevention of microvascular and neuropathic complications. However, tight glycemic control is still difficult to achieve using current available regimen, and therefore novel pathogenesis‐based interventions that can prevent and reverse the complications even in the presence of hyperglycemia are needed. Over the past decade, advances in molecular and cellular biological techniques have revealed many potential mechanisms utilized by hyperglycemia to induce its adverse effects. Several mechanisms, including vascular oxidative stress; formation of advanced glycation endproducts; activation of protein kinase C; increased flux through hexosamine pathway; inflammation‐induced vascular pathology; altered expression and actions of growth factors, cytokines, and vasomotor mediators; and increased flux through polyol pathway, have been studied in detail. The identification of such mechanisms has lead to the development of novel pharmacological approaches.

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Connective Tissue Growth Factor and Regulation of the Mesangial Cell Cycle

Cited by 108 publications

References 73 publications

Transcriptome Profiling and the Pathogenesis of Diabetic Complications

Transcriptome Profiling and the Pathogenesis of Diabetic Complications

TGF-β1-induced PINCH-1-ILK-α-parvin complex formation regulates mesangial cell proliferation and hypertrophy

Pathogenesis of Diabetic Microvascular Complications

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