PP2A protects podocytes against Adriamycin-induced injury and epithelial-to-mesenchymal transition via suppressing JIP4/p38-MAPK pathway View Full Text


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Article Info

DATE

2021-08-13

AUTHORS

Zhihong Lu, Xiujuan Zhu, Yuhong Ye, Haidong Fu, Jianhua Mao

ABSTRACT

Protein phosphatase 2A (PP2A) is one of the major protein serine/threonine phosphatases (PPPs) with regulatory effects on several cellular processes, but its role and function in Adriamycin (ADR)-treated podocytes injury needs to be further explored. Mice podocytes were treated with ADR and PP2A inhibitor (okadaic acid, OA). After transfection, cell apoptosis was detected by flow cytometry. Expressions of podocytes injury-, apoptosis- and epithelial-to-mesenchymal transition (EMT)- and JNK-interacting protein 4/p38-Mitogen-Activated Protein Kinase (JIP4/p38-MAPK) pathway-related factors were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. Interaction between PP2A and JIP4/MAPK pathway was confirmed using co-immunoprecipitation (Co-Ip) assay. In podocytes, ADR inhibited PP2A, Nephrin and Wilms’ tumor (WT) 1 expressions yet upregulated apoptosis and Desmin expression, and suppressing PP2A expressionenhanced the effects. PP2A overexpression reversed the effects of ADR on PP2A and podocyte injury-related factors expressions and apoptosis of podocytes. JIP4 was the candidate gene interacting with both PP2A and p38-MAPK pathway, and PP2A overexpression alleviated the effects of ADR on p38-MAPK pathway-related factors expressions. Additionally, in ADR-treated podocytes, PP2A suppression enhanced the effects of ADR, yet silencing of JIP4 reversed the effects of PP2A suppression on regulating p38-MAPK pathway-, apoptosis- and EMT-related factors expressions and apoptosis, with upregulations of B-cell lymphoma-2 (Bcl-2) and E-cadherin and down-regulations of Bcl-2 associated protein X (Bax), cleaved (C)-casapse-3, N-cadherin, Vimentin and Snail. PP2A protects ADR-treated podocytes against injury and EMT by suppressing JIP4/p38-MAPK pathway, showing their interaction in podocytes. More... »

PAGES

697-713

References to SciGraph publications

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  • 2018-07-23. CD155 downregulation synergizes with adriamycin to induce breast cancer cell apoptosis in APOPTOSIS
  • 2019-08-06. Protein phosphatase 2A modulates podocyte maturation and glomerular functional integrity in mice in CELL COMMUNICATION AND SIGNALING
  • 2019-03-28. The role of podocyte damage in the etiology of ischemia-reperfusion acute kidney injury and post-injury fibrosis in BMC NEPHROLOGY
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  • 2017-11-17. TFEB regulates lysosomal positioning by modulating TMEM55B expression and JIP4 recruitment to lysosomes in NATURE COMMUNICATIONS
  • 2016-11-28. Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3β/β-catenin signaling pathways in ACTA PHARMACOLOGICA SINICA
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    http://scigraph.springernature.com/pub.10.1007/s10616-021-00484-1

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    http://dx.doi.org/10.1007/s10616-021-00484-1

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34629746


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