Renal expression of the C3a receptor and functional responses of primary human proximal tubular epithelial cells.
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.
Braun
Michael C
MC
Center for Immunology, Brown Foundation Institute of Molecular Medicine, University of Texas, Houston 77030, USA. michael.c.braun@uth.tmc.edu
Reins
Rose Y
RY
Li
Tong-Bin
TB
Hollmann
Travis J
TJ
Dutta
Ranjan
R
Rick
Wetsel A
WA
Teng
Ba-Bie
BB
Ke
Baozhen
B
D000818:Animals; D003167:Complement Activation / Q000235:genetics / Q000276:immunology; D015926:Complement C3a / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007678:Kidney Glomerulus / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D011951:Receptors, Complement / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D014158:Transcription, Genetic / Q000276:immunology
D008565:Membrane Proteins; D012333:RNA, Messenger; D011951:Receptors, Complement; C085567:complement C3a receptor; D015926:Complement C3a