| First Author | Takahashi S | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 305 |
| Issue | 6 | Pages | F861-70 |
| PubMed ID | 23842779 | Mgi Jnum | J:200930 |
| Mgi Id | MGI:5510281 | Doi | 10.1152/ajprenal.00597.2012 |
| Citation | Takahashi S, et al. (2013) SIRPalpha signaling regulates podocyte structure and function. Am J Physiol Renal Physiol 305(6):F861-70 |
| abstractText | Signal-regulatory protein-alpha (SIRPalpha) is a transmembrane protein that contains tyrosine phosphorylation sites in its cytoplasmic region; two tyrosine phosphatases, SHP-1 and SHP-2, bind to these sites in a phosphorylation-dependent manner and transduce multiple intracellular signals. Recently, SIRPalpha was identified as one of the major tyrosine-phosphorylated proteins in the glomeruli and found to be expressed in podocytes. In the present study, we examined the role of SIRPalpha expression in podocytes using knockin mice (C57BL/6 background) expressing mutant SIRPalpha that lacks a cytoplasmic region (SIRPalpha-mutant mice). Light microscopic examination revealed no apparent morphological abnormalities in the kidneys of the SIRPalpha-mutant mice. On the other hand, electron microscopic examination revealed abnormal podocytes with irregular major processes and wider and flattened foot processes in the SIRPalpha-mutant mice compared with their wild-type counterparts. Significantly impaired renal functions and slight albuminuria were demonstrated in the SIRPalpha-mutant mice. In addition, adriamycin injection induced massive albuminuria together with focal glomerulosclerosis in the SIRPalpha-mutant mice, while their wild-type counterparts were resistant to adriamycin-induced nephropathy. These data demonstrate that SIRPalpha is involved in the regulation of podocyte structure and function as a filtration barrier under both physiological and pathological conditions. |
