SIRP<b>α</b> interacts with nephrin at the podocyte slit diaphragm

Kajiho, Yuko; Harita, Yutaka; Kurihara, Hidetake; Horita, Shigeru; Matsunaga, Atsuko; Tsurumi, Haruko; Kanda, Shoichiro; Sato, Noriko; Miura, Kenichiro; Sekine, Takashi; Hattori, Satoshi; Hattori, Motoshi; Igarashi, Takashi

doi:10.1111/j.1742-4658.2012.08682.x

Cited by 18 publications

(9 citation statements)

References 40 publications

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“…Podocyte nephrin disintegration in the slit diaphragm has been observed to contribute to loss of protein excretion [17]. Nephrin has been shown to act as a protein tyrosine kinase that triggers biologic reaction in maintaining podocyte function and renal filtration capacity in various renal disorders [18][19][20]. And a recent paper demonstrated that diabetes led to a reduction in the nephrin level in conjunction with nephrin deacetylation [21].…”

Section: Discussionmentioning

confidence: 96%

Pentraxin-3 Attenuates Renal Damage in Diabetic Nephropathy by Promoting M2 Macrophage Differentiation

et al. 2015

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As one of the most important long-term complications of diabetes, diabetic nephropathy (DN) is the major cause of end-stage renal disease and high mortality in diabetic patients. The long pentraxin 3 (Ptx3) is a member of a superfamily of conserved proteins characterized by a cyclic multimeric structure and a conserved C-terminal domain. Several clinical investigations have demonstrated that elevated plasma Ptx3 levels are associated with cardiovascular and chronic kidney diseases (CKD). However, the therapeutic effect of Ptx3 on DN has never been investigated. In our current study, we showed a crucial role for Ptx3 in attenuating renal damage in DN. In our mouse hyperglycemia-induced nephropathy model, Ptx3 treatment showed significantly increased expression of nephrin, acetylated nephrin, and Wilm's tumor-1 protein (WT-1) when compared with control. The number of CD4(+) T cells, CD8(+) T cells, Ly6G(+) neutrophils, and CD11b(+) macrophages were all significantly lower in the Ptx3-treated group than that in the control group in DN. The IL-4 and IL-13 levels in the Ptx3-treated group were markedly higher than that in the control group in DN. Correspondingly, the Ptx3-treated group showed increased numbers of Arg1- or CD206-expressing macrophages compared with the control group. Furthermore, inhibition of Ptx3-treated macrophages abrogated the alleviated renal damage induced by Ptx3 treatment. In conclusion, Ptx3 attenuates renal damage in DN by promoting M2 macrophage differentiation.

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Section: Discussionmentioning

confidence: 96%

Pentraxin-3 Attenuates Renal Damage in Diabetic Nephropathy by Promoting M2 Macrophage Differentiation

et al. 2015

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“…Until now, the expression of SIRP␣ in podocytes has been reported in rats and humans but not in mice (11,14,33). Therefore, we are the first to determine the expression of SIPR␣ in mouse podocytes.…”

Section: Resultsmentioning

confidence: 96%

“…Immunofluorescence microscopic and immunoelectron microscopic examinations have shown that SIRP␣ is predominantly localized in the foot processes of the podocytes (33). In addition, the direct interaction of SIRP␣ and nephrin was demonstrated in vivo and in vitro (11). In the current study, we further examined the role of SIRP␣ in maintaining the structure and function of podocytes using knockin mice expressing mutant SIRP␣ that lacks the cytoplasmic domain containing four putative tyrosine-phosphorylated sites (SIRP␣-mutant mice) ( Fig.…”

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confidence: 86%

SIRPα signaling regulates podocyte structure and function

Takahashi

Tomioka

Hiromura

et al. 2013

American Journal of Physiology-Renal Physiology

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Signal-regulatory protein-α (SIRPα) 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, SIRPα 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 SIRPα expression in podocytes using knockin mice (C57BL/6 background) expressing mutant SIRPα that lacks a cytoplasmic region (SIRPα-mutant mice). Light microscopic examination revealed no apparent morphological abnormalities in the kidneys of the SIRPα-mutant mice. On the other hand, electron microscopic examination revealed abnormal podocytes with irregular major processes and wider and flattened foot processes in the SIRPα-mutant mice compared with their wild-type counterparts. Significantly impaired renal functions and slight albuminuria were demonstrated in the SIRPα-mutant mice. In addition, adriamycin injection induced massive albuminuria together with focal glomerulosclerosis in the SIRPα-mutant mice, while their wild-type counterparts were resistant to adriamycin-induced nephropathy. These data demonstrate that SIRPα is involved in the regulation of podocyte structure and function as a filtration barrier under both physiological and pathological conditions.

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“…Podocyte nephrin disintegration in the slit diaphragm has been observed to contribute to loss of protein excretion [1]. Nephrin has been shown to act as a protein tyrosin kinase that triggers biologic reaction in maintaining podocyte function and renal filtration capacity in various renal disorders [14][15][16]. And recent paper demonstrated that diabetes led to a reduction in the nephrin level in conjunction with nephrin deacetylation [17].…”

Section: Discussionmentioning

confidence: 95%

MicroRNA-155 Deficiency Promotes Nephrin Acetylation and Attenuates Renal Damage in Hyperglycemia-Induced Nephropathy

et al. 2014

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MiR-155 has been reported to be involved in both innate and adaptive immune responses. But the role of miR-155 in hyperglycemia-induced nephropathy is still unknown. In our current study, 3-month-old male wild-type C57 mice and Mir-155(-/-) mice were used to establish hyperglycemia-induced nephropathy. In our hyperglycemia-induced nephropathy model, the expression of podocyte injury marker desmin was markedly increased in the diabetes group when compared with control. Diabetes also significantly decreased the levels of nephrin and acetylated nephrin, whereas the expression of miR-155 was markedly increased in diabetes group when compared with control. MiR-155(-/-) mice showed significantly increased expression of nephrin, acetylated nephrin, and Wilm's tumor-1 protein (WT-1) when compared with wild-type control. MiR-155 deficiency results in significantly decrease in IL-17A expression both in vivo and in vitro. And the increased expression of WT-1, nephrin, and ac-nephrin was reversed with additional treatment of rmIL-17. Furthermore, we found that the inhibited Th17 differentiation induced by miR-155 deficiency was dependent on increased expression of SOCS1. In conclusion, miR-155 deficiency promotes nephrin acetylation and attenuates renal damage in hyperglycemia-induced nephropathy. This was associated with inhibited IL-17 production through enhancement of SOCS1 expression.

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SIRPα interacts with nephrin at the podocyte slit diaphragm

Cited by 18 publications

References 40 publications

Pentraxin-3 Attenuates Renal Damage in Diabetic Nephropathy by Promoting M2 Macrophage Differentiation

Pentraxin-3 Attenuates Renal Damage in Diabetic Nephropathy by Promoting M2 Macrophage Differentiation

SIRPα signaling regulates podocyte structure and function

MicroRNA-155 Deficiency Promotes Nephrin Acetylation and Attenuates Renal Damage in Hyperglycemia-Induced Nephropathy

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