Cross‐talk between transmembrane signalling systems: a prerequisite for the delicate regulation of glomerular haemodynamics by mesangial cells

Pfeilschifter, Josef

doi:10.1111/j.1365-2362.1989.tb00241.x

Cited by 105 publications

(70 citation statements)

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Together with increased extracellular matrix production and inflammatory mediator secretion, mesangial cell proliferation is a hallmark of many forms of glomerulonephritis ultimately leading to glomerulosclerosis (1,2). The detailed mechanisms regulating cell proliferation, however, are still not completely understood, although the involvement of the mitogen-activated protein kinase (MAPK) 1 cascade is generally assumed (4 -6).…”

mentioning

confidence: 99%

“…Renal mesangial cells not only play an important physiological role in the regulation of glomerular filtration rate but also importantly contribute to most pathological processes of the renal glomerulus (1)(2)(3). Together with increased extracellular matrix production and inflammatory mediator secretion, mesangial cell proliferation is a hallmark of many forms of glomerulonephritis ultimately leading to glomerulosclerosis (1,2).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Sphingosine 1-Phosphate Cross-activates the Smad Signaling Cascade and Mimics Transforming Growth Factor-β-induced Cell Responses

Xin

Ren

Kleuser

et al. 2004

Journal of Biological Chemistry

171

143

View full text Add to dashboard Cite

Exposure of renal mesangial cells to sphingosine 1-phosphate (S1P) leads to a rapid and transient activation of the mitogen-and stress-activated protein kinases but also the protein kinase B. Here, we show that S1P also induces phosphorylation of Smad proteins, which are members of the transforming growth factor-␤ (TGF-␤) signaling device. However, Smad phosphorylation occurred more slowly with a maximal effect after 20 -30 min of S1P stimulation when compared with the rapid activation of the MAPKs. Interestingly, Smad phosphorylation is increased by pertussis toxin, which is in contrast to the complete inhibition of S1P-induced MAPK phosphorylation by pertussis toxin. TGF-␤ is a potent anti-inflammatory cytokine, which in mesangial cells attenuates the expression of (i) inducible nitricoxide synthase (iNOS) caused by interleukin (IL)-1␤, (ii) secreted phospholipase A 2 (sPLA 2 ), and (iii) matrix metalloproteinase-9 (MMP-9). These gene products are also down-regulated by S1P in a concentration-dependent manner. Furthermore, the expression of connective tissue growth factor is enhanced by both TGF-␤ 2 and S1P. These effects of S1P are not mediated by the MAPK cascade as neither pertussis toxin nor the MAPK cascade inhibitor U0126 are able to reverse this inhibition. Overexpression of the inhibitory Smad-7 or down-regulation of co-Smad-4 lead to a reversal of the blocking effect of S1P on IL-1␤-induced NO release. Moreover, down-regulating the TGF-␤ receptor type II by the siRNA technique or antagonizing the S1P 3 receptor subtype with suramin abrogates S1P-stimulated Smad phosphorylation. In summary, our data show that S1P trans-activates the TGF-␤ receptor and triggers activation of Smads followed by activation of connective tissue growth factor gene transcription and inhibition of IL-1␤-induced expression of iNOS, sPLA 2 , and MMP-9.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Sphingosine 1-Phosphate Cross-activates the Smad Signaling Cascade and Mimics Transforming Growth Factor-β-induced Cell Responses

Xin

Ren

Kleuser

et al. 2004

Journal of Biological Chemistry

171

143

View full text Add to dashboard Cite

show abstract

“…We propose that only a small proportion of the whole cell population is susceptible to cyclic AMP-induced apoptosis at a certain time point. However, since mesangial cells have a prominent phagocytic capacity [3] the overall degree of apoptotic cell death may be underestimated because apoptotic cells are likely to be phagocytosed rapidly by their neighbours. The molecular mechanism of cyclic AMP-induced apoptosis is not known, but the intracellular transduction mechanism is believed to be exclusively protein kinase A mediated [18].…”

Section: Discussionmentioning

confidence: 99%

“…Several mediators are known to act on glomerular mesangial cells by stimulating the cyclic AMP signalling pathway. Examples are histamine, adenosine, prostaglandin E2, dopamine and others (for review see [3]). Recently Baker et al [5] reported that mesangial cell apoptosis is induced during the course of Thy-1 nephritis in rats.…”

Section: B Ementioning

confidence: 99%

“…Mesangial cells located within the renal glomerulus are regarded as specialized smooth muscle cells, involved in the regulation of the glomerular filtration rate [3]. Moreover, once activated in a proinflammatory context mesangial cells release a variety of proinflammatory mediators and growth factors, thus being an important determinant of the immunological status of the renal glomerulus and contributing to glomerular pathophysiology [4].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Apoptosis is triggered by the cyclic AMP signalling pathway in renal mesangial cells

et al. 1996

View full text Add to dashboard Cite

Glomerular mesangial cells are regarded as specialized smooth muscle cells located within the renal glomeruli and fulfilling important functions in glomerular physiology and pathophysiology. Here, we report that activation of the cyclic AMP signalling pathway by dibutyryl cyclic AMP, forskolin, or the ~2-adrenergic receptor agonist salbutamol results in induction of apoptosis in mesangial cells. Activation of the apoptotic programme results in DNA fragmentation which is visible for most forms of apoptosis and is paralleled by enrichment of cytosolic DNA/histone complexes, an increasing number of cellular 3'-OH-fragmented DNA ends and typical nuclear chromatin condensation. Induction of apoptosis was found to be dependent on translation and independent of nitric oxide synthase activity.Key words: Apoptosis; Cyclic AMP; Forskolin; Salbutamol; Mesangial cells characterize cellular signals which initiate the apoptotic programme in mesangial cells. Here we present evidence that activation of the cyclic AMP signalling pathway results in mesangial cell apoptosis in a translation-dependent and nitric oxide synthase-independent manner.

show abstract

Thy-1-Mediated phosphatidylinositol turnover in cultured rat glomerular mesangial cell

et al. 1996

View full text Add to dashboard Cite

Thy-1 glycoprotein is expressed in rat glomerular mesangial cells, and anti-Thy-1 nephritis induced by anti-Thy-1 antibodies is a model of human renal diseases. In this study, we examined Thy-1-mediated biological reactions in cultured rat glomerular mesangial cells utilizing two anti-Thy-1 monoclonal antibodies (mAbs), 1-22-3 and OX-7. Incubation of the cells with these mAbs resulted in increased inositol trisphosphate (IP3) levels. The rise in IP3 produced by mAb 1-22-3 was greater than that produced by mAb OX-7 at the same dose. Incubation of mesangial cells with these mAbs resulted in an increase in the intracellular free calcium concentration ([Ca2+]i). mAb 1-22-3 induced a sustained increase in [Ca2+]i, while that induced by mAb OX-7 lasted 1-2 min, then decreased to the basal level. An transient increase in [Ca2+]i was also observed in Ca(2+)-free medium, indicating that these [Ca2+]i increases are due to release of Ca2+ from internal stores by IP3 without calcium flux across cell membrane. When cells were pretreated with protein tyrosine kinase (PTK) inhibitors (herbimycin A or genistein), Thy-1-mediated increases in [Ca2+]i were inhibited. These data suggest that Thy-1 induces the production of IP3 (including inositol 1,4,5-triphosphate, an intracellular Ca(2+)-releasing factor) and that PTKs may contribute to the Thy-1-mediated elevation of [Ca2+]i which presumably results from phospholipase C activation following Thy-1-mediated signaling in rat mesangial cells.

show abstract

Cross‐talk between transmembrane signalling systems: a prerequisite for the delicate regulation of glomerular haemodynamics by mesangial cells

Cited by 105 publications

References 128 publications

Sphingosine 1-Phosphate Cross-activates the Smad Signaling Cascade and Mimics Transforming Growth Factor-β-induced Cell Responses

Sphingosine 1-Phosphate Cross-activates the Smad Signaling Cascade and Mimics Transforming Growth Factor-β-induced Cell Responses

Apoptosis is triggered by the cyclic AMP signalling pathway in renal mesangial cells

Thy-1-Mediated phosphatidylinositol turnover in cultured rat glomerular mesangial cell

Contact Info

Product

Resources

About