SIRPα signaling regulates podocyte structure and function

Takahashi, Satoshi; Tomioka, Mai; Hiromura, Keiju; Sakairi, Toru; Hamatani, Hiroko; Watanabe, Mitsuharu; Ikeuchi, Hidekazu; Kaneko, Yoriaki; Maeshima, Akito; Aoki, Takeo; Ohnishi, Hiroshi; Matozaki, Takashi; Nojima, Yoshihisa

doi:10.1152/ajprenal.00597.2012

Cited by 10 publications

(6 citation statements)

References 34 publications

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“…The level of the glomerular protein SIRPA was already decreased in the db/db vehicle mice compared to the healthy db/+ vehicle mice and insulin decreased the abundance even further. It has been shown to interact with nephrin in the slit diaphragm of the podocyte [ 38 ] and could be involved in podocyte injury [ 39 ]. Insulin also significantly decreased the abundance of GPR116 similar to SIRPA in the db/db mice (Fig.…”

Section: Discussionmentioning

confidence: 99%

N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models

et al. 2016

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BackgroundDiabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. These glycosylated proteins are highly important in cell adhesion and cell–matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances.MethodWe enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses.ResultsThe majority of the N-glycosylated proteins were similarly regulated in both mouse models. However, distinct differences between the two mouse models were for example seen for integrin-β1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice.ConclusionsOur finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell–matrix composition in T1DM and T2DM. Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-016-9123-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models

et al. 2016

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“…The binding of macrophage SIRPα to its widely expressed ligand, CD47, induces an inhibitory signal for phagocytosis, a “don’t eat me” signal 21 that prevents the phagocytosis of healthy cells. Mice with genetic inactivation or mutation of SIRPα have numerous abnormalities, including impairment of phagocyte migration 22 , dendritic cell (DCs) homeostasis 23 , bone cell differentiation 24 , kidney function 25 , and interleukin (IL)-17 and interferon (IFN)-γ production 26 . Phagocytes from SIRPα mutant mice also have enhanced respiratory bursts 27 .…”

Section: Introductionmentioning

confidence: 99%

A functional subset of CD8+ T cells during chronic exhaustion is defined by SIRPα expression

Myers¹,

Tal

Dulgeroff

et al. 2019

Nat Commun

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Prolonged exposure of CD8+ T cells to antigenic stimulation, as in chronic viral infections, leads to a state of diminished function termed exhaustion. We now demonstrate that even during exhaustion there is a subset of functional CD8+ T cells defined by surface expression of SIRPα, a protein not previously reported on lymphocytes. On SIRPα+ CD8+ T cells, expression of co-inhibitory receptors is counterbalanced by expression of co-stimulatory receptors and it is only SIRPα+ cells that actively proliferate, transcribe IFNγ and show cytolytic activity. Furthermore, target cells that express the ligand for SIRPα, CD47, are more susceptible to CD8+ T cell-killing in vivo. SIRPα+ CD8+ T cells are evident in mice infected with Friend retrovirus, LCMV Clone 13, and in patients with chronic HCV infections. Furthermore, therapeutic blockade of PD-L1 to reinvigorate CD8+ T cells during chronic infection expands the cytotoxic subset of SIRPα+ CD8+ T cells.

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“…Albuminuria is one the most common symptoms in people with obesity-associated glomerular injury, which is characterized as glomeruli enlargement, focal segmental glomerulosclerosis, basement membrane thickening, and podocyte damage [3]. Recent studies focusing on podocyte physiology have indicated that podocyte structural and functional integrity is required for preventing glomerular albumin leakage and subsequent albuminuria [4, 5]. Previous study suggested that high glucose-induced oxidative stress initiated podocyte apoptosis and depletion both in vivo and in vitro [6], which represents an early mechanism driving diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 99%

Interaction of thrombospondin1 and CD36 contributes to obesity-associated podocytopathy

Cui¹,

Maimaitiyiming²,

Zhou³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Obesity is associated with podocyte injury and the development of proteinuria. Elevated plasma free fatty acid is one of the characteristics of obesity and has been linked to podocyte dysfunction. However, the mechanisms remain unclear. In the current study, we examined the effect of saturated free fatty acid (FFA) on human podocyte apoptosis and function in vitro. The mechanism and its in vivo relevance were also determined. We found that FFA treatment induced human podocyte apoptosis and dysfunction, which was associated with increased expression of a matricellualr protein-thrombospondin1 (TSP1). FFA stimulated TSP1 expression in podocytes at the transcriptional levels through activation of MAPK pathway. Addition of purified TSP1 to cell culture media induced podocyte apoptosis and dysfunction. Tis effect is though a TGF-β independent mechanism. Moreover, peptide treatment to block TSP1 binding to its receptor-CD36 attenuated FFA induced podocyte apoptosis, suggesting that TSP1/CD36 interaction mediates FFA-induced podocyte apoptosis. Importantly, using a dietinduced obese mouse model, in vivo data demonstrated that obesity-associated podocyte apoptosis and dysfunction were attenuated in TSP1 deficient mice as well as in CD36 deficient mice. Taken together, these studies provide novel evidence that the interaction of TSP1 with its receptor CD36 contributes to obesity - associated podocytopathy.

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SIRPα signaling regulates podocyte structure and function

Cited by 10 publications

References 34 publications

N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models

N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models

A functional subset of CD8+ T cells during chronic exhaustion is defined by SIRPα expression

Interaction of thrombospondin1 and CD36 contributes to obesity-associated podocytopathy

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