PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachment
Podocytes play a critical role in maintaining normal glomerular filtration, and podocyte loss from the glomerular basement membrane (GBM) initiates and worsens chronic kidney disease (CKD). However, the exact mechanism underlying podocyte loss remains unclear. Fructose-2,6-biphosphatase 3 (PFKFB3) i...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2023.2230318 |
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| author | Xiaoxiao Huang Zhaowei Chen Zilv Luo Yiqun Hao Jun Feng Zijing Zhu Xueyan Yang Zongwei Zhang Jijia Hu Wei Liang Guohua Ding |
| author_facet | Xiaoxiao Huang Zhaowei Chen Zilv Luo Yiqun Hao Jun Feng Zijing Zhu Xueyan Yang Zongwei Zhang Jijia Hu Wei Liang Guohua Ding |
| author_sort | Xiaoxiao Huang |
| collection | DOAJ |
| description | Podocytes play a critical role in maintaining normal glomerular filtration, and podocyte loss from the glomerular basement membrane (GBM) initiates and worsens chronic kidney disease (CKD). However, the exact mechanism underlying podocyte loss remains unclear. Fructose-2,6-biphosphatase 3 (PFKFB3) is a bifunctional enzyme that plays crucial roles in glycolysis, cell proliferation, cell survival, and cell adhesion. This study aimed to determine the role of PFKFB3 in angiotensin II (Ang II) kidney damage. We found that mice infused with Ang II developed glomerular podocyte detachment and impaired renal function accompanied by decreased PFKFB3 expression in vivo and in vitro. Inhibition of PFKFB3 with the PFKFB3 inhibitor 3PO further aggravated podocyte loss induced by Ang II. In contrast, activating PFKFB3 with the PFKFB3 agonist meclizine alleviated the podocyte loss induced by Ang II. Mechanistically, PFKFB3 knockdown likely aggravate Ang II-induced podocyte loss by suppressing talin1 phosphorylation and integrin beta1 subunit (ITGB1) activity. Conversely, PFKFB3 overexpression protected against Ang II-induced podocyte loss. These findings suggest that Ang II leads to a decrease in podocyte adhesion by suppressing PFKFB3 expression, and indicates a potential therapeutic target for podocyte injury in CKD. |
| format | Article |
| id | doaj-art-e852fc2f9fdc4f97a4066615f29b1449 |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-e852fc2f9fdc4f97a4066615f29b14492025-08-20T03:53:07ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492023-12-0145110.1080/0886022X.2023.2230318PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachmentXiaoxiao Huang0Zhaowei Chen1Zilv Luo2Yiqun Hao3Jun Feng4Zijing Zhu5Xueyan Yang6Zongwei Zhang7Jijia Hu8Wei Liang9Guohua Ding10Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, ChinaDivision of Nephrology, Renmin Hospital of Wuhan University, Wuhan, ChinaDivision of Nephrology, Renmin Hospital of Wuhan University, Wuhan, ChinaDivision of Nephrology, Renmin Hospital of Wuhan University, Wuhan, ChinaDivision of Nephrology, Renmin Hospital of Wuhan University, Wuhan, ChinaDivision of Nephrology, Renmin Hospital of Wuhan University, Wuhan, ChinaDivision of Nephrology, Renmin Hospital of Wuhan University, Wuhan, ChinaDivision of Nephrology, Renmin Hospital of Wuhan University, Wuhan, ChinaDivision of Nephrology, Renmin Hospital of Wuhan University, Wuhan, ChinaDivision of Nephrology, Renmin Hospital of Wuhan University, Wuhan, ChinaDivision of Nephrology, Renmin Hospital of Wuhan University, Wuhan, ChinaPodocytes play a critical role in maintaining normal glomerular filtration, and podocyte loss from the glomerular basement membrane (GBM) initiates and worsens chronic kidney disease (CKD). However, the exact mechanism underlying podocyte loss remains unclear. Fructose-2,6-biphosphatase 3 (PFKFB3) is a bifunctional enzyme that plays crucial roles in glycolysis, cell proliferation, cell survival, and cell adhesion. This study aimed to determine the role of PFKFB3 in angiotensin II (Ang II) kidney damage. We found that mice infused with Ang II developed glomerular podocyte detachment and impaired renal function accompanied by decreased PFKFB3 expression in vivo and in vitro. Inhibition of PFKFB3 with the PFKFB3 inhibitor 3PO further aggravated podocyte loss induced by Ang II. In contrast, activating PFKFB3 with the PFKFB3 agonist meclizine alleviated the podocyte loss induced by Ang II. Mechanistically, PFKFB3 knockdown likely aggravate Ang II-induced podocyte loss by suppressing talin1 phosphorylation and integrin beta1 subunit (ITGB1) activity. Conversely, PFKFB3 overexpression protected against Ang II-induced podocyte loss. These findings suggest that Ang II leads to a decrease in podocyte adhesion by suppressing PFKFB3 expression, and indicates a potential therapeutic target for podocyte injury in CKD.https://www.tandfonline.com/doi/10.1080/0886022X.2023.2230318Angiotensin IIpodocytePFKFB3adhesion |
| spellingShingle | Xiaoxiao Huang Zhaowei Chen Zilv Luo Yiqun Hao Jun Feng Zijing Zhu Xueyan Yang Zongwei Zhang Jijia Hu Wei Liang Guohua Ding PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachment Renal Failure Angiotensin II podocyte PFKFB3 adhesion |
| title | PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachment |
| title_full | PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachment |
| title_fullStr | PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachment |
| title_full_unstemmed | PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachment |
| title_short | PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachment |
| title_sort | pfkfb3 downregulation aggravates angiotensin ii induced podocyte detachment |
| topic | Angiotensin II podocyte PFKFB3 adhesion |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2023.2230318 |
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