Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization

Abe, Katsushige; Miyazaki, Masanobu; Koji, Takehiko; Furusu, Akira; Nakamura-Kurashige, Tomomi; Nishino, Tomoya; Ozono, Yoshiyuki; Harada, Takashi; Sakai, Hideto; Kohno, Shigeru

doi:10.1046/j.1523-1755.2001.00780.x

Cited by 65 publications

(55 citation statements)

References 42 publications

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“…The renal distribution of the C3aR is similar to that reported for C5aR (22,23,25). In regard to C5aR, published reports indicate that the pattern of expression of this receptor is altered in disease states with up-regulation in glomerular mesangial cells (26). This finding suggests that further investigation into the distribution of the C3aR in pathologic conditions is warranted.…”

Section: Discussionsupporting

confidence: 77%

Renal Expression of the C3a Receptor and Functional Responses of Primary Human Proximal Tubular Epithelial Cells

Braun¹,

Reins²,

et al. 2004

The Journal of Immunology

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Although complement activation and deposition have been associated with a variety of glomerulopathies, the pathogenic mechanisms by which complement directly mediates renal injury remain to be fully elucidated. Renal parenchymal tissues express a limited repertoire of receptors that directly bind activated complement proteins. We report the renal expression of the receptor for the C3 cleavage product C3a, a member of the anaphylatoxin family. C3aR is highly expressed in normal human and murine kidney, as demonstrated by immunohistochemistry and in situ hybridization. Its distribution is limited to epithelial cells only, as glomerular endothelial and mesangial cells showed no evidence of C3aR expression. The C3aR is also expressed by primary renal proximal tubular epithelial cells in vitro as demonstrated by FACS, Western blot, and RT-PCR. In vitro C3aR is functional in terms of its capacity to bind 125I-labeled C3a and generate inositol triphosphate. Finally, using microarray analysis, four novel genes were identified and confirmed as transcriptionally regulated by C3aR activation in proximal tubular cells. These studies define a new pathway by which complement activation may directly modulate the renal response to immunologic injury.

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Section: Discussionsupporting

confidence: 77%

Renal Expression of the C3a Receptor and Functional Responses of Primary Human Proximal Tubular Epithelial Cells

Braun¹,

Reins²,

et al. 2004

The Journal of Immunology

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“…These include immune complexinduced peritonitis [30], experimental arthritis [31], sepsis [32] and anti-phospholipid syndrome [33]. C5aR mRNA has been found to be up-regulated in glomeruli of patients with lupus nephritis, supporting its relevance in the human disease [20]. Here we have shown that the overexpression of both C5aR mRNA and protein in MRL/ lpr mouse kidneys started before the onset of detectable disease, and increased as autoimmune disease progressed, suggesting a potential role for C5a and C5aR signals in the pathogenesis of this disease.…”

Section: Discussionmentioning

confidence: 97%

“…Of relevance to the kidney is the finding of C5aR in cultured renal mesangial and proximal tubular epithelial cells [16][17][18], and that C5a signaling through C5aR has been shown to be important in the tubulointerstitial injury in a model of immune complex-mediated glomerulonephritis (GN) [19]. As for humans, the expression of C5aR has been observed to be increased in the kidneys of patients with lupus nephritis [20], supporting its potential relevance in disease pathogenesis. Yet, direct studies on the role of C5a and C5aR in the pathogenesis of lupus nephritis have not been performed.…”

Section: Introductionmentioning

confidence: 97%

C5a promotes development of experimental lupus nephritis which can be blocked with a specific receptor antagonist

et al. 2005

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“…C5aR expression in the skin lesions of patients with systemic sclerosis suggests an activation of pathways that end up with a growth factor-dependent matrix synthesis (31). In mesangial proliferative glomerulonephritis, the glomerular expression of C5aR mRNA and protein correlate positively with the extent of mesangial hypercellularity and mesangial matrix expansion (32). In rheumatoid arthritis, i.e., another condition with inflammatory and proliferative stages, some chondrocytes express C5aR (33, 34) that argues for a contribution of this receptor in arthritis pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Expression of a Functional C5a Receptor in Regenerating Hepatocytes and Its Involvement in a Proliferative Signaling Pathway in Rat

Daveau

Bénard

Scotté

et al. 2004

The Journal of Immunology

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Activation of the complement system generates the anaphylatoxin C5a whose activities are mediated through its binding to the widely expressed C5aR. C5aR mRNA and protein expressions are known to be induced in rat hepatocytes under inflammatory conditions. However, little is known about the role of the C5a/C5aR complex in liver and its involvement during a proliferative process. We have evaluated the expression of C5aR in regenerating rat hepatocytes following a partial hepatectomy and in hepatocyte cultures. C5aR induction was observed in hepatocytes from regenerating liver, as well as in normal hepatocytes under a culture-induced stress. The effect of a stimulation by a C5a agonist upon the synthesis of a growth factor/receptor pair (hepatocyte growth factor/c-Met) was also evaluated. Our data demonstrated an up-regulated expression of hepatocyte growth factor and c-Met mRNAs, but we failed to observe a direct mitogenic effect of C5a in culture. However, a significantly increased expression of cyclin E and D1mRNA levels, as well as an increased BrdU incorporation, were observed in rats given an i.v. C5a agonist injection following an 80% partial hepatectomy. These studies demonstrate for the first time that: 1) C5aR is up-regulated during liver regeneration, 2) the binding of C5a to C5aR promotes a growth response, and 3) C5aR is involved in a cell cycle signaling pathway. Taken together, these findings point to a novel role for the hepatic C5aR implicating this complement system in the context of normal or abnormal proliferative pathways.

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Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization

Abstract: Our results indicate that renal cells produce C5aR and that activation of C5a/C5aR pathway on renal cells may be involved in tissue injury in mesGN.

Cited by 65 publications

References 42 publications

Renal Expression of the C3a Receptor and Functional Responses of Primary Human Proximal Tubular Epithelial Cells

Renal Expression of the C3a Receptor and Functional Responses of Primary Human Proximal Tubular Epithelial Cells

C5a promotes development of experimental lupus nephritis which can be blocked with a specific receptor antagonist

Expression of a Functional C5a Receptor in Regenerating Hepatocytes and Its Involvement in a Proliferative Signaling Pathway in Rat

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