TGF-β in Glomerular Disease

Shankland, Stuart J.; Johnson, Richard J.

doi:10.1159/000057366

Cited by 22 publications

(17 citation statements)

References 49 publications

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“…However, hyperlipidemia did induce tubulointerstitial influx of macrophages/foam cells, presumably mediated by chemoattractants other than MCP-1. Studies have also indicated that macrophages from hyperlipidemic rats may be a major source for increased TGF-b expression [23,24], an important cytokine for mediating extracellular matrix deposition [53]. Our study also demonstrated a significant correlation between glomerular macrophage content and TGF-b expression.…”

Section: Discussionsupporting

confidence: 73%

Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice

Mühlfeld¹,

Spencer²,

Hudkins³

et al. 2004

Kidney International

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Section: Discussionsupporting

confidence: 73%

Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice

Mühlfeld¹,

Spencer²,

Hudkins³

et al. 2004

Kidney International

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“…TGF-b plays an important role in the pathogenesis of glomerular disease and mediates extracellular matrix deposition leading to glomerulosclerosis (Shankland and Johnson, 1998). However, TGF-b is also known to inhibit cell mitogenesis of a variety of cells including renal cells.…”

mentioning

confidence: 99%

Eicosapentaenoic acid inhibits PDGF‐induced mitogenesis and cyclin D1 expression via TGF‐β in mesangial cells

Hida

Fujita

Ishikura

et al. 2003

Journal Cellular Physiology

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Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid derived from fish oil, is efficacious in glomerular diseases where mesangial proliferation is a key event. We examined the mechanisms of action of EPA on platelet-derived growth factor (PDGF)-stimulated rat mesangial cell mitogenesis. EPA dose-dependently inhibited PDGF-stimulated [(3)H]-thymidine incorporation. PDGF-induced PDGF receptor autophosphorylation, an initial event for PDGF signaling, was not affected by 2 micro g/ml EPA. Similarly, PDGF-stimulated activation of extracellular signal-regulated kinase (ERK) was not altered. On the other hand, EPA inhibited cyclin-dependent kinase 4 (CDK4) activation and cyclin D1 protein induction, a critical step for G1/S progression. TGF-beta secretion assessed by ELISA and bioassay was increased by EPA at 18 h. Coincubation with anti-TGF-beta antibody inhibited the EPA-induced suppression of [(3)H]-thymidine incorporation and cyclin D1 expression. SB203580, an inhibitor of p38, a downstream kinase of TGF-beta, did not affect EPA's growth inhibitory effect. These results demonstrate that EPA inhibits PDGF-stimulated mesangial cell mitogenesis and cyclin D1 expression via TGF-beta.

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“…Transforming growth factor-␤ (TGF-␤) is an important cytokine in renal disease (1,2). TGF-␤ mediates extracellular matrix protein accumulation, cell proliferation, and hypertrophy, and it also regulates the immune response.…”

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confidence: 99%

The Hypertrophic Effect of Transforming Growth Factor-β is Reduced in the Absence of Cyclin-Dependent Kinase-Inhibitors p21 and p27

Monkawa¹,

Hiromura²,

Wolf³

et al. 2002

Journal of the American Society of Nephrology

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ABSTRACT. Transforming growth factor-β (TGF-β) has both antiproliferative and hypertrophic effects on mesangial cells (MC). However, it is not known if these processes are independent or if they share common signaling pathways. Proliferation and hypertrophy are regulated by specific cell-cycle regulatory proteins, where the cyclin-dependent kinase (CDK) inhibitors inhibit target cyclin-CDK complexes. This study examined whether the growth regulatory effects of TGF-β were determined by the CDK inhibitors p21 and p27. Accordingly, cultured MC from wild type (+/+) and single and double null (−/−) p21 and p27 mice were grown in 5% serum in the presence or absence of TGF-β1 (2 ng/ml). Proliferation ([3H]-thymidine incorporation, cell number, cell cycle) and hypertrophy ([3H]-leucine incorporation, total protein content, forward light scatter) were measured after 24 h, 48 h, and 96 h. TGF-β inhibited proliferation in +/+ and p21/p27 double −/− MC to a similar extent. TGF-β induced hypertrophy in +/+ MC (18.0% increase at 48 h), and to lesser extent in p21 −/− (12.8%) and p27 −/− MC (11.5%) measured by forward light scatter analysis. In p21/p27 double −/−, the hypertrophic effects of TGF-β were significantly reduced (3.9% at 48 h). Similar results were obtained by measuring hypertrophy by total protein and [3H]-leucine incorporation. In conclusion, the CDK inhibitors p21 and p27 are not required for the antiproliferative effects of TGF-β. However, the hypertrophic growth effects of TGF-β are reduced in the absence of both p21 and p27. These data suggest that the regulation of the antiproliferative and hypertrophic effects of TGF-β may be distinct processes.

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TGF-β in Glomerular Disease

Cited by 22 publications

References 49 publications

Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice

Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice

Eicosapentaenoic acid inhibits PDGF‐induced mitogenesis and cyclin D1 expression via TGF‐β in mesangial cells

The Hypertrophic Effect of Transforming Growth Factor-β is Reduced in the Absence of Cyclin-Dependent Kinase-Inhibitors p21 and p27

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