Inhibition of nephrin activation by c-mip through Csk–Cbp–Fyn axis plays a critical role in Angiotensin II-induced podocyte damage

Liu, Yu; Lin, Qiuxia; Feng, Jianhua; Dong, Xiaohong; Liu, Qifeng; Ye, Jianming

doi:10.1016/j.cellsig.2012.11.017

Cited by 26 publications

(28 citation statements)

References 25 publications

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“…Therefore, Akt is regarded as an apoptosis suppressor factor and was used in our study. As in a previous study (Yu et al, 2013), our study showed that overexpression of Fyn can significantly increase Akt and p-Akt treated with SW. The results indicate that Fyn can promote the activation of Akt and then protect against apoptosis by regulating the expression of Akt phosphorylation.…”

Section: Discussionsupporting

confidence: 88%

Fyn arrests swainsonine-induced apoptosis in 293T cells via Akt and its phosphorylation

Cheng

2015

Genet. Mol. Res.

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ABSTRACT. Swainsonine (SW), an extract from Astragalus membranaceus, represents a new class of compounds that inhibit growth and induce apoptosis in a cancer model. In this study, we demonstrated the effect of Fyn on SW-induced apoptosis in 293T cells. Western blotting was used to measure the expression of the apoptosis-related factors caspase-3, Bcl-2, Bax, and the key factor Akt (also known as protein kinase B). Apoptosis increased dramatically after treatment with SW. Unlike the control group, after transfection with Fyn, the expression of Bcl-2, in contrast to Bax, was markedly upregulated. The results also showed that the protein expression levels of Akt and phosphorylated Akt were markedly increased. Our results establish that Fyn can arrest SW-induced apoptosis via the activity of Akt and its effective phosphorylation in 293T cells.

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Section: Discussionsupporting

confidence: 88%

Fyn arrests swainsonine-induced apoptosis in 293T cells via Akt and its phosphorylation

Cheng

2015

Genet. Mol. Res.

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“…1F), indicating an induction of c-mip in glomerular podocyte by ADR. Up-regulation of c-mip was also reported in angiotensin II-mediated podocyte injury [24]. Interestingly, the increase of c-mip mRNA in PBMC occurred earlier than that in kidney glomerular in AN mice (Fig.…”

Section: Discussionmentioning

confidence: 84%

Induction of C-Mip by IL-17 Plays an Important Role in Adriamycin-Induced Podocyte Damage

Yan-Bo

Lin

et al. 2015

Cell Physiol Biochem

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Background/Aims: Although the disturbance of T lymphocyte and glomerular podocyte exerts a crucial function in the pathogenesis of proteinuria, the potential link is still unclear. Methods: The balance of Treg and Th17 cells, and the expression of IL-17/IL-17R and c-mip were investigated in adrimycin-induced nephropathy (AN) mice. The effect and mechanism of IL-17 on podocyte were explored in cultured podocytes. Results: The proportion of Th17 cells in peripheral blood mononuclear cells, the amount of IL-17 in serum and kidney cortical homogenates, and the expression of IL-17R and c-mip in glomerular podocyte were increased obviously in AN mice. In cultured podocytes, recombinant IL-17 led to an induction of apoptosis and cytoskeletal disorganization, an overproduction of c-mip while down-regulation of phosphor-nephrin, and an increased binding of c-mip to NF-κB/RelA. Silence of c-mip prevented podocyte apoptosis and reduction of phosphor-nephrin by prompting nuclear translocation of NF-κB/RelA in IL-17 treated cells. Persistent activation of NF-κB up-regulated pro-survival protein Bcl-2 and decreased podocyte apoptosis, but had no effect on phosphor-nephrin level. Conclusion: These findings demonstrated that induction of IL-17 released by Th17 cells plays a key role in podocytopathy most likely through down-regulation of phosphor-nephrin and Bcl-2 level via overproduction of c-mip.

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“…AngII is one of the crucial factors in chronic kidney disease and podocyte injury. 6,7 We found AngII-induced cytoskeleton disruption and nuclear translocation of Cabin1 in cultured podocytes. These results indicated Cabin1 undergone nuclear translocation during podocyte injury.…”

Section: Disscussionmentioning

confidence: 79%

“…1 Recently, a great deal of SD molecules, which relates to podocyte injury have been recognized, including nephrin, podocin, CD2AP, and TRPC6, etc. 2,3 Angiotensin-II (AngII) is an important risk factor in podocyte injury, researchers found it promoted podocyte apoptosis both in vitro and in vivo [4][5][6][7] AngII binds to cell surface G protein-coupled receptors (GPCR), which couple to heterotrimeric G proteins of the Gq/11 family. 8 Gq enhances podocyte apoptosis in a calcineurin (CaN)-dependent fashion, while the activation of CaN could be blocked by CaN inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Cabin1 localizes in glomerular podocyte and undergoes nuclear translocation during podocyte injury

et al. 2015

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(2015) Cabin1 localizes in glomerular podocyte and undergoes nuclear translocation during podocyte injury, Renal Failure, 37:8, 1344-1348 Department of General Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China Abstract Context: Podocyte injury is related to increasing proteinuria and contributes to the progression of kidney disease. Calcineurin binding protein 1 (Cabin1) is a repressor of myocyte enhancer factor 2 (MEF2) and calcineurin-mediated transcription in the immune system. Moreover, Cabin1 interacts with p53 and negatively regulates p53 in tumor cells. However, its function in kidney is unknown. Objective: To explore the exact localization of Cabin1 in glomeruli, as well as the relationship between Cabin1 and podocyte injury. Methods: Sprague-Dawley rats were sacrificed to observe the localization and protein expression of Cabin1 in the kidney. Cabin1 localization and protein expression were detected by immunofluorescence staining and western blot, respectively. Mouse podocytes were cultivated at 33 C to propagate, then cells were transferred to an incubator at 37 C to allow differentiation. Differentiated podocytes were stimulated by angiotensin II (AngII) or AngII plus tacrolimus. Cells were harvested to detect the localization and protein expression of Cabin1. Cytoplasmic and nuclear protein were separated by protein extraction kit. Results: Cabin1 mainly localized in the nuclei of glomerular innate cells, it colocalized with WT-1 in podocytes nuclei. Western bolt showed Cabin1 protein remarkably expressed in renal cortex. AngII-induced Cabin1 nuclear protein significantly increased, accompanied by cytoskeleton disruption in cultured mouse podocytes. Conclusion: Cabin1 localizes in glomerular podocytes. AngII induces nuclear translocation of Cabin1 in cultured podocytes.

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Inhibition of nephrin activation by c-mip through Csk–Cbp–Fyn axis plays a critical role in Angiotensin II-induced podocyte damage

Cited by 26 publications

References 25 publications

Fyn arrests swainsonine-induced apoptosis in 293T cells via Akt and its phosphorylation

Fyn arrests swainsonine-induced apoptosis in 293T cells via Akt and its phosphorylation

Induction of C-Mip by IL-17 Plays an Important Role in Adriamycin-Induced Podocyte Damage

Cabin1 localizes in glomerular podocyte and undergoes nuclear translocation during podocyte injury

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