Thrombospondin 1 is expressed by proliferating mesangial cells and is up-regulated by PDGF and bFGF in vivo

Hugo, Christian; Pichler, Raimund; Meek, Rick L.; Gordon, Katherine; Kyriakides, Themis R.; Floege, Jürgen; Börnstein, Paul; Couser, William G.; Johnson, Richard J.

doi:10.1038/ki.1995.483

Cited by 76 publications

(80 citation statements)

References 38 publications

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“…Fibronectin is present basally within the mesangial matrix functioning in supporting mesangial cell viability, 35 increases in fibronectin have been demonstrated in fibrotic disease processes. 36 TSP is transiently expressed in matrix during development and repair 23,37 and has previously been shown to respond to PDGF, TGF-␤ 1 , and basic fibroblast growth factor, 37 it is a known regulator of TGF-␤ 1 activity. 23,38 We further verify that levels of decorin, a small leucine-rich proteoglycan that acts as an endogenous inhibitor of TGF-␤ 1, 39 are decreased in response to PDGF and are recovered by LXA 4 pretreatment.…”

Section: Discussionmentioning

confidence: 99%

Lipoxin A4 Modifies Platelet-Derived Growth Factor-Induced Profibrotic Gene Expression in Human Renal Mesangial Cells

Rodgers

McMahon

Mitchell

et al. 2005

The American Journal of Pathology

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Lipoxins (LXs), endogenously produced eicosanoids, possess potent anti-inflammatory, proresolution bioactivities. We investigated the potential of LXA 4 (1 to 10 nmol/L) to modify the effects of platelet-derived growth factor (PDGF)-induced gene expression in human renal mesangial cells (hMCs). Using oligonucleotide microarray analysis we profiled profibrotic cytokines and matrix-associated genes induced in response to PDGF. LXA 4 modulated the expression of many PDGF-induced genes, including transforming growth factor-␤1, fibronectin, thrombospondin, matrix metalloproteinase 1, and several collagens. Analysis of both transcript and protein levels confirmed these findings. Because the activated glomerulus is frequently a source of injurious mediators that contribute to tubulointerstitial damage, we investigated the effect of hMC-secreted products on the integrity of renal proximal tubular epithelial cells using an in vitro model of progressive renal disease. Cell supernatant from PDGF-stimulated hMCs caused morphological and genetic changes in proximal tubular epithelial cells, consistent with a profibrotic phenotype. Interestingly, supernatant from cells pre-exposed to LXA 4 and PDGF did not induce these effects. These results suggest a novel role for LXA 4

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Section: Discussionmentioning

confidence: 99%

Lipoxin A4 Modifies Platelet-Derived Growth Factor-Induced Profibrotic Gene Expression in Human Renal Mesangial Cells

Rodgers

McMahon

Mitchell

et al. 2005

The American Journal of Pathology

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“…Glomerular preparations were done by the standard sieving procedure as described previously. 25 Biopsies from healthy human and mouse kidneys Normal human renal tissue (n ¼ 6) was obtained from kidneys surgically excised because of the presence of a localized neoplasm. Tissues utilized for this study were obtained from macroscopically normal portions of kidney located at some distance from the neoplastic process.…”

Section: Materials and Methods Animal Modelmentioning

confidence: 99%

“…25 As secondary antibody, we used a rat adsorbed biotinylated horse anti-mouse IgG (Vector, Burlingame, USA), which was detected by horseradish peroxidase-conjugated avidin D (Vector). The peroxidase substrate 3,3 0 -diaminobenzidine (substrate kit; Vector) was used without nickel resulting in a brown staining (nestin) and Histogreen (Vector) was used for green nuclear staining (PCNA).…”

Section: Immunohistochemical Double Stainingsmentioning

confidence: 99%

Nestin expression in repopulating mesangial cells promotes their proliferation

Daniel

Albrecht

Lüdke

et al. 2008

Laboratory Investigation

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We investigated whether the intermediate filament protein and neural stem cell marker nestin characterizes the glomerular progenitor/reserve cell population immigrating the glomerulus after mesangial cell (MC) injury in the rat (antiThy1 nephritis). Nestin expression was investigated by immunohistochemistry and real-time PCR during anti-Thy1 nephritis. Migration and proliferation assays were used to characterize the function of nestin in isolated MCs after nestin knockdown by siRNA. After MC injury during anti-Thy1 nephritis, glomerular nestin was transiently increased during the repopulation phase. At the peak of mesangial proliferation and expansion (day 5) most OX-7-positive MCs expressed nestin largely colocalizing with the activation marker a-smooth muscle actin and the proliferation marker PCNA. In contrast to a healthy, non-injured mesangium in vivo, MCs in culture are considered to be in an 'activated, injured state' and express nestin in a generalized distribution with condensed localization around the nucleus as well as intensive staining of cell protrusions such as filopodia. During cell cycle, the percentage of MCs with high nestin levels was increased during S-and G2-phase. Blocking of nestin using specific siRNA resulted in inhibition of cell proliferation but not cell migration. In conclusion, nestin is constitutively expressed in podocytes, but is a marker for repopulating MCs after experimental MC injury in vivo. Nestin promotes MC proliferation in vitro, suggesting a supporting role for nestin during repair reaction.

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“…Immunoperoxidase staining for ␣-smooth muscle actin was performed with a murine IgG 2 monoclonal antibody (21) (Sigma) essentially as described previously (22,23). The primary antibody was incubated overnight at 4°C, followed sequentially by biotinylated rabbit antimouse IgG (Zymed Laboratories Inc.), avidin D peroxidase, and finally diaminobenzidine without nickel chloride.…”

Section: Methodsmentioning

confidence: 99%

Proliferating and Migrating Mesangial Cells Responding to Injury Express a Novel Receptor Protein-tyrosine Phosphatase in Experimental Mesangial Proliferative Glomerulonephritis

Wright¹,

Hugo²,

Seifert³

et al. 1998

Journal of Biological Chemistry

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The mesangial cell provides structural support to the kidney glomerulus. A polymerase chain reaction-based cDNA display approach identified a novel protein-tyrosine phosphatase, rPTP-GMC1, whose transcript expression is transiently and dramatically up-regulated during the period of mesangial cell migration and proliferation that follows mesangial cell injury in the anti-Thy 1 model of mesangial proliferative glomerulonephritis in the rat. In situ hybridization analysis confirmed that rPTP-GMC1 mRNA is up-regulated specifically by mesangial cells responding to the injury and is not detectable in other cells in the kidney or in many normal tissues. In cell culture, rPTP-GMC1 is expressed by mesangial cells but not by glomerular endothelial or epithelial cells (podocytes). The longest transcript (7.5 kilobases) encodes a receptor-like protein-tyrosine phosphatase consisting of a single catalytic domain, a transmembrane segment, and 18 fibronectin type IIIlike repeats in the extracellular segment. A splice variant predicts a truncated molecule missing the catalytic domain. rPTP-GMC1 maps to human chromosome 12q15 and to the distal end of mouse chromosome 10. The predicted structure of rPTP-GMC1 and its pattern of expression in vivo and in culture suggest that it plays a role in regulating the adhesion and migration of mesangial cells in response to injury.

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Thrombospondin 1 is expressed by proliferating mesangial cells and is up-regulated by PDGF and bFGF in vivo

Cited by 76 publications

References 38 publications

Lipoxin A4 Modifies Platelet-Derived Growth Factor-Induced Profibrotic Gene Expression in Human Renal Mesangial Cells

Lipoxin A4 Modifies Platelet-Derived Growth Factor-Induced Profibrotic Gene Expression in Human Renal Mesangial Cells

Nestin expression in repopulating mesangial cells promotes their proliferation

Proliferating and Migrating Mesangial Cells Responding to Injury Express a Novel Receptor Protein-tyrosine Phosphatase in Experimental Mesangial Proliferative Glomerulonephritis

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