Phosphoinositide 3 Kinase γ Plays a Critical Role in Acute Kidney Injury
Inflammatory cells contribute to the pathogenesis of renal ischemia-reperfusion injury (IRI). However, the signaling mechanisms underlying the infiltration of inflammatory cells into the kidney are not well understood. In this study, we examined the effects of phosphoinositide 3 kinase γ (PI3Kγ) on...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/5/772 |
| _version_ | 1797475416921866240 |
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| author | Xiaogao Jin Qinjun Chu Liwei Sun Melanie Tran Yanlin Wang |
| author_facet | Xiaogao Jin Qinjun Chu Liwei Sun Melanie Tran Yanlin Wang |
| author_sort | Xiaogao Jin |
| collection | DOAJ |
| description | Inflammatory cells contribute to the pathogenesis of renal ischemia-reperfusion injury (IRI). However, the signaling mechanisms underlying the infiltration of inflammatory cells into the kidney are not well understood. In this study, we examined the effects of phosphoinositide 3 kinase γ (PI3Kγ) on inflammatory cells infiltration into the kidney in response to ischemia-reperfusion injury. Compared with wild-type mice, PI3Kγ knockout mice displayed less IRI in the kidney with fewer tubular apoptotic cell. Furthermore, PI3Kγ deficiency decreased the number of infiltrated neutrophils, macrophages, and T cells in the kidney, which was accompanied by a decrease in the expression of pro-inflammatory cytokines in the kidney. Moreover, wild-type mice treated with AS-605240, a selective PI3Kγ inhibitor, displayed less tubular damage, accumulated fewer inflammatory cells, and expressed less proinflammatory molecules in the kidney following IRI. These results demonstrate that PI3Kγ has a critical role in the pathogenesis of kidney damage in IRI, indicating that PI3Kγ inhibition may serve as a potential therapeutic strategy for the prevention of ischemia-reperfusion-induced kidney injury. |
| first_indexed | 2024-03-09T20:44:47Z |
| format | Article |
| id | doaj.art-83c7acea711f44b590ab5e7efc1f810a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:44:47Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-83c7acea711f44b590ab5e7efc1f810a2023-11-23T22:50:03ZengMDPI AGCells2073-44092022-02-0111577210.3390/cells11050772Phosphoinositide 3 Kinase γ Plays a Critical Role in Acute Kidney InjuryXiaogao Jin0Qinjun Chu1Liwei Sun2Melanie Tran3Yanlin Wang4Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, ChinaDepartment of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, ChinaDepartment of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, ChinaDivision of Nephrology, Department of Medicine and Department of Cell Biology, University of Connecticut School of Medicine, Farmington, CT 06030, USASection of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USAInflammatory cells contribute to the pathogenesis of renal ischemia-reperfusion injury (IRI). However, the signaling mechanisms underlying the infiltration of inflammatory cells into the kidney are not well understood. In this study, we examined the effects of phosphoinositide 3 kinase γ (PI3Kγ) on inflammatory cells infiltration into the kidney in response to ischemia-reperfusion injury. Compared with wild-type mice, PI3Kγ knockout mice displayed less IRI in the kidney with fewer tubular apoptotic cell. Furthermore, PI3Kγ deficiency decreased the number of infiltrated neutrophils, macrophages, and T cells in the kidney, which was accompanied by a decrease in the expression of pro-inflammatory cytokines in the kidney. Moreover, wild-type mice treated with AS-605240, a selective PI3Kγ inhibitor, displayed less tubular damage, accumulated fewer inflammatory cells, and expressed less proinflammatory molecules in the kidney following IRI. These results demonstrate that PI3Kγ has a critical role in the pathogenesis of kidney damage in IRI, indicating that PI3Kγ inhibition may serve as a potential therapeutic strategy for the prevention of ischemia-reperfusion-induced kidney injury.https://www.mdpi.com/2073-4409/11/5/772PI3Kγacute kidney injuryinflammationischemia-reperfusion injury |
| spellingShingle | Xiaogao Jin Qinjun Chu Liwei Sun Melanie Tran Yanlin Wang Phosphoinositide 3 Kinase γ Plays a Critical Role in Acute Kidney Injury Cells PI3Kγ acute kidney injury inflammation ischemia-reperfusion injury |
| title | Phosphoinositide 3 Kinase γ Plays a Critical Role in Acute Kidney Injury |
| title_full | Phosphoinositide 3 Kinase γ Plays a Critical Role in Acute Kidney Injury |
| title_fullStr | Phosphoinositide 3 Kinase γ Plays a Critical Role in Acute Kidney Injury |
| title_full_unstemmed | Phosphoinositide 3 Kinase γ Plays a Critical Role in Acute Kidney Injury |
| title_short | Phosphoinositide 3 Kinase γ Plays a Critical Role in Acute Kidney Injury |
| title_sort | phosphoinositide 3 kinase γ plays a critical role in acute kidney injury |
| topic | PI3Kγ acute kidney injury inflammation ischemia-reperfusion injury |
| url | https://www.mdpi.com/2073-4409/11/5/772 |
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