Cultured rat glomerular epithelial cells show gene expression and production of transforming growth factor‐β: expression is enhanced by thrombin

Tsunoda, Satoru; Yamabe, Hideaki; Osawa, Hiroshi; Kaizuka, Mitsuaki; Shirato, Kenichi; Okumura, Ken

doi:10.1093/ndt/16.9.1776

Cited by 17 publications

(19 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, TGF-␤ inhibited podocyte proliferation. Therefore, thrombin and perhaps other vasoactive hormones may play a role in the progression of glomerulosclerosis through the upregulation of TGF-␤ production in podocytes (468). However, nothing is known about possible effects of ANG II on MAP kinases, phospholipase D, and phospholipase A 2 ; induction of protooncogene expression; cross-talk with tyrosine kinase receptors; stimulation of nuclear signaling cascades; and production of other growth factors, which might modulate long-term functions of podocytes.…”

Section: Ca 2؉ Signalingmentioning

confidence: 99%

See 1 more Smart Citation

Cell Biology of the Glomerular Podocyte

Pavenstädt

Kriz

Kretzler

2003

Physiological Reviews

1,322

1,278

View full text Add to dashboard Cite

Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. New technical approaches have led to a considerable increase in our understanding of podocyte biology including protein inventory, composition and arrangement of the cytoskeleton, receptor equipment, and signaling pathways involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of acquired glomerular disease. In hereditary nephrotic syndromes identified over the last 2 years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.

show abstract

Section: Ca 2؉ Signalingmentioning

confidence: 99%

“…Podocytes have been shown to secrete TGF-␤ in response to several agents such as high glucose (475), low-density lipoprotein (94), or thrombin (468). Mice that are transgenic for an active form of TGF-␤1 develop progressive glomerulosclerosis with mesangial expansion and thickened capillary loops after 3 wk of age.…”

Section: E Tgf-␤mentioning

confidence: 99%

Cell Biology of the Glomerular Podocyte

Pavenstädt

Kriz

Kretzler

2003

Physiological Reviews

1,322

1,278

View full text Add to dashboard Cite

show abstract

“…Recent in vitro studies have shown that GEC are capable of secreting TGFβ1 [20], PDGF [21] and Angiotensin II [22], factors that may mediate glomerular injury. Of these three, TGFβ1 is the most potent profibrogenic factor in glomerular cells.…”

Section: Introductionmentioning

confidence: 99%

ERK-dependent Signaling Pathway and Transcriptional Factor Ets-1 Regulate Matrix Metalloproteinase-9 Production in Transforming Growth Factor-β1 Stimulated Glomerular Podocytes

Liu

Liang

Huang

et al. 2005

Cell Physiol Biochem

View full text Add to dashboard Cite

The unregulated synthesis of glomerular basement membrane (GBM) components, extracelluar matrix (ECM) proteins, or the secretion of ECM-degradation enzymes, matrix metalloproteinases (MMPs), by podocytes under pathological conditions might be major factors in GBM damage. The present study examined the effects and the underlying molecular mechanism of transforming growth factor β1 (TGFβ1) on the production of gelatinase in cultured murine podocytes. Our results showed that TGFβ1 is the most potent inducer of MMP-9 secretion in both a dose- and time-dependent manner, but has very little effect on MMP-2 secretion. TGFβ1 upregulated MMP-9 mRNA levels, but did not affect the expression of matrix mettaloproteinases TIMP-1 mRNA. TGFβ1 induced activation of both Smad2 and extracellular signal-regulated kinases (ERK1/2). However, blockade of Smad2 signaling pathway by Staurosporine did not affect the TGFβ1-stimulated secretion of MMP-9, whereas inhibition of activation of ERK1/2 by PD98059 abolished TGFβ1-stimulated secretion of MMP-9 and expression of MMP-9 mRNA. Protein levels of the transcriptional factor Ets-1 increased and were sustained for 12 h by TGFβ1-stimulation. Our data also showed that blockage of ERK1/2 activation by PD98059 led to a reduction in the level of Ets-1 protein and to a consequent decrease in MMP-9 mRNA levels. These results demonstrate that TGFβ1 can induce the production of MMP-9 in podocytes through the ERK1/2 MAPK pathway, and suggested that an increase in MMP-9 enzymatic activities may be involved in the damage of the GBM in response to inflammatory factors, ultimately leading to glomerulosclerosis.

show abstract

“…16) We have also reported that thrombin mediated various factors. [17][18][19][20][21][22] In the previous study, we showed that thrombin increased the production of MCP-1 and MIP-2 by GEC and enhanced mRNA of these cytokines. 23) It is well known that neutrophils are involved in acute phase of inflammation and following macrophages infiltrate.…”

Section: Discussionmentioning

confidence: 99%

Mizoribine Suppresses Proliferation of Rat Glomerular Epithelial Cells in Culture and Inhibits Increase of Monocyte Chemoattractant Protein-1 and Macrophage Inflammatory Protein-2 Stimulated by Thrombin

Yamabe

Shimada

Murakami

et al. 2012

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

Cultured rat glomerular epithelial cells show gene expression and production of transforming growth factor‐β: expression is enhanced by thrombin

Abstract: Rat GEC produce TGF-beta in vitro. Thrombin may participate in the progression of glomerulosclerosis in crescentic glomerulonephritis through the stimulation of TGF-beta production by GEC.

Cited by 17 publications

References 27 publications

Cell Biology of the Glomerular Podocyte

Cell Biology of the Glomerular Podocyte

ERK-dependent Signaling Pathway and Transcriptional Factor Ets-1 Regulate Matrix Metalloproteinase-9 Production in Transforming Growth Factor-β1 Stimulated Glomerular Podocytes

Mizoribine Suppresses Proliferation of Rat Glomerular Epithelial Cells in Culture and Inhibits Increase of Monocyte Chemoattractant Protein-1 and Macrophage Inflammatory Protein-2 Stimulated by Thrombin

Contact Info

Product

Resources

About