Mechanisms of TGF-β signaling in regulation of cell growth and differentiation

Moustakas, Aristidis; Pardali, Katerina; Gaál, A; Heldin, Carl Henrik

doi:10.1016/s0165-2478(02)00023-8

Cited by 488 publications

(392 citation statements)

References 54 publications

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“…53,54 By associating with the cyclin D1-CDK4 complexes and suppressing their kinase activity, these inhibitors are able to sequester the complexes in an inactive state. As a result of the combination effect of inhibitors and the direct TGF-␤-mediated cyclin D1-CDK4 down-regulation, treated VICs have mostly underphosphorylated active tumor suppressor proteins that contribute to the growth retardation.…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor-β Regulates the Growth of Valve Interstitial Cells in Vitro

Gotlieb

2011

The American Journal of Pathology

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Although valve interstitial cell (VIC) growth is an essential feature of injured and diseased valves, the regulation of VIC growth is poorly understood. Transforming growth factor (TGF)-␤ promotes VIC proliferation in early-stage wound repair; thus, herein, we tested the hypothesis that TGF-␤ regulates VIC proliferation under normal nonwound conditions using low-density porcine VIC monolayers. Cell numbers were counted during a 10-day period, whereas proliferation and apoptosis were quantified by bromodeoxyuridine staining and TUNEL, respectively. The extent of retinoblastoma protein phosphorylation and expression of cyclin D1, CDK 4, and p27 were compared using Western blot analysis. Adhesion was quantified using a trypsin adhesion assay, and morphological change was demonstrated by immunofluorescence localization of ␣-smooth muscle actin and vinculin. TGF-␤-treated VICs were rhomboid; significantly decreased in number, proliferation, and retinoblastoma protein phosphorylation; and concomitantly had decreased expression of cyclin D1/CDK4 and increased expression of p27. TGF-␤-treated VICs adhered better to substratum and had more vinculin plaques and ␣-smooth muscle actin stress fibers than did controls. Thus, the regulation of VIC growth by TGF-␤ is context dependent. TGF-␤ prevents excessive heart valve growth under normal physiological conditions while it promotes cell proliferation in the early stages of repair, when increased VICs are required.

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Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor-β Regulates the Growth of Valve Interstitial Cells in Vitro

Gotlieb

2011

The American Journal of Pathology

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“…Genes in the TGF-b/BMP pathway were initally chosen as candidate genes because of its role in cell proliferation, tissue repair, the immune, and the inflammatory response [reviewed in [32][33][34]. We hypothesized that these and other candidate genes might modulate the pathobiology of sickle cell disease.…”

Section: Discussionmentioning

confidence: 99%

Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B

Nolan

Cohen

et al. 2006

American J Hematol

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Renal disease is common in sickle cell anemia. In this exploratory work, we used data from a longitudinal study of the natural history of sickle cell disease to examine the hypothesis that polymorphisms (SNPs) in selected candidate genes are associated with glomerular filtration rate (GFR). DNA samples and clinical and laboratory data were available for 1,140 patients with sickle cell anemia. GFR was estimated using the Cockcroft-Gault and Schwartz formulas for adults and children, respectively. We examined *175 haplotype tagging (ht) SNPs in about 70 genes of the TGFb/BMP pathway for their association with GFR using linear regression. Four SNPs in BMPR1B, a bone morphogenetic protein (BMP) receptor gene, yielded statistically significant associations (P values ranging from 0.015 to 0.046). Three haplotypes in this gene were also associated with GFR. The TGF-b/BMP pathway has been associated with the development of diabetic nephropathy, which has some features in common with sickle cell nephropathy. Our results suggest that, as with other subphenotypes of sickle cell disease, renal function may be genetically modulated. Am. J. Hematol. 82:179-184, 2007. V V C 2006 Wiley-Liss, Inc.

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“…15 In line with this, TGF-β induces cell cycle proteins such as p21, which suppress cell division, and it suppresses the degradation of matrix proteins as reviewed elsewhere. 33,34 However, TGF-β2 does not affect expression of more advanced contractile phenotype markers such as SM-MHC and smoothelin. 15 The TGF-β-like factor activin A also stimulates expression of contractile marker proteins such as α-SMA and SM22α.…”

Section: Biochemical Factorsmentioning

confidence: 99%

Regulation and characteristics of vascular smooth muscle cell phenotypic diversity

Rensen¹,

Doevendans²,

Eys³

2007

NHJL

776

706

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Vascular smooth muscle cells can perform both contractile and synthetic functions, which are associated with and characterised by changes in morphology, proliferation and migration rates, and the expression of different marker proteins. The resulting phenotypic diversity of smooth muscle cells appears to be a function of innate genetic programmes and environmental cues, which include biochemical factors, extracellular matrix components, and physical factors such as stretch and shear stress. Because of the diversity among smooth muscle cells, blood vessels attain the flexibility that is necessary to perform efficiently under different physiological and pathological conditions. In this review, we discuss recent literature demonstrating the extent and nature of smooth muscle cell diversity in the vascular wall and address the factors that affect smooth muscle cell phenotype. (Neth Heart J 2007;15:100-8.)

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Mechanisms of TGF-β signaling in regulation of cell growth and differentiation

Cited by 488 publications

References 54 publications

Transforming Growth Factor-β Regulates the Growth of Valve Interstitial Cells in Vitro

Transforming Growth Factor-β Regulates the Growth of Valve Interstitial Cells in Vitro

Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B

Regulation and characteristics of vascular smooth muscle cell phenotypic diversity

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