Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress
Acute kidney injury (AKI) is a serious clinical disease that is mainly caused by renal ischemia-reperfusion (I/R) injury, sepsis, and nephrotoxic drugs. The pathologic mechanism of AKI is very complex and may involve oxidative stress, inflammatory response, autophagy, apoptosis, and endoplasmic reti...
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00147/full |
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| author | Xiaohua Tan Qianyu Tao Qianyu Tao Guixiu Li Lijun Xiang Xiaomeng Zheng Xiaomeng Zheng Tianzhen Zhang Cuijiao Wu Dequan Li |
| author_facet | Xiaohua Tan Qianyu Tao Qianyu Tao Guixiu Li Lijun Xiang Xiaomeng Zheng Xiaomeng Zheng Tianzhen Zhang Cuijiao Wu Dequan Li |
| author_sort | Xiaohua Tan |
| collection | DOAJ |
| description | Acute kidney injury (AKI) is a serious clinical disease that is mainly caused by renal ischemia-reperfusion (I/R) injury, sepsis, and nephrotoxic drugs. The pathologic mechanism of AKI is very complex and may involve oxidative stress, inflammatory response, autophagy, apoptosis, and endoplasmic reticulum (ER) stress. The basic fibroblast growth factor (FGF2) is a canonic member of the FGF family that plays a crucial role in various cellular processes, including organ development, wound healing, and tissue regeneration. However, few studies have reported the potential therapeutic effect of FGF2 in the repair of renal ischemic injury in the past two decades. In the present study, we investigated the protective effect of FGF2 on renal I/R injury using Sprague-Dawley and NRK-52E cells. Our results showed that FGF2 significantly attenuates the apoptosis of kidney tissues after I/R injury through the inhibition of excessive ER stress. Moreover, FGF2 also alleviated the excessive ER stress and apoptosis in cultured NRK-52E cells injured by tert-Butyl hydroperoxide (TBHP). Significantly, phosphatidylinositol 3-kinase (PI3K)-selective inhibitor LY294002 and mitogen-activated protein kinase kinase (MEK)-selective inhibitor U0126 were utilized in the present study to examine the protective mechanism of FGF2. Our in vitro experimental results confirmed that both LY294002 and U0126 largely abolished the protective effect of FGF2. Taken together, the findings of the present study indicated that FGF2 attenuates I/R-induced renal epithelial apoptosis by suppressing excessive ER stress via the activation of the PI3K/AKT and MEK-ERK1/2 signaling pathways. |
| first_indexed | 2024-12-10T06:00:28Z |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-10T06:00:28Z |
| publishDate | 2020-03-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-47cd7f599fb14d10a7fbda3a27d5804b2022-12-22T01:59:49ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-03-01810.3389/fcell.2020.00147506810Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum StressXiaohua Tan0Qianyu Tao1Qianyu Tao2Guixiu Li3Lijun Xiang4Xiaomeng Zheng5Xiaomeng Zheng6Tianzhen Zhang7Cuijiao Wu8Dequan Li9Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaBeilun District People’s Hospital of Ningbo, Ningbo, ChinaOutpatient Operating Room, Jiaozhou Central Hospital of Qingdao, Qingdao, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaSchool of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, ChinaBeilun District People’s Hospital of Ningbo, Ningbo, ChinaDepartment of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, ChinaDepartment of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, ChinaDepartment of Traumatology Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaAcute kidney injury (AKI) is a serious clinical disease that is mainly caused by renal ischemia-reperfusion (I/R) injury, sepsis, and nephrotoxic drugs. The pathologic mechanism of AKI is very complex and may involve oxidative stress, inflammatory response, autophagy, apoptosis, and endoplasmic reticulum (ER) stress. The basic fibroblast growth factor (FGF2) is a canonic member of the FGF family that plays a crucial role in various cellular processes, including organ development, wound healing, and tissue regeneration. However, few studies have reported the potential therapeutic effect of FGF2 in the repair of renal ischemic injury in the past two decades. In the present study, we investigated the protective effect of FGF2 on renal I/R injury using Sprague-Dawley and NRK-52E cells. Our results showed that FGF2 significantly attenuates the apoptosis of kidney tissues after I/R injury through the inhibition of excessive ER stress. Moreover, FGF2 also alleviated the excessive ER stress and apoptosis in cultured NRK-52E cells injured by tert-Butyl hydroperoxide (TBHP). Significantly, phosphatidylinositol 3-kinase (PI3K)-selective inhibitor LY294002 and mitogen-activated protein kinase kinase (MEK)-selective inhibitor U0126 were utilized in the present study to examine the protective mechanism of FGF2. Our in vitro experimental results confirmed that both LY294002 and U0126 largely abolished the protective effect of FGF2. Taken together, the findings of the present study indicated that FGF2 attenuates I/R-induced renal epithelial apoptosis by suppressing excessive ER stress via the activation of the PI3K/AKT and MEK-ERK1/2 signaling pathways.https://www.frontiersin.org/article/10.3389/fcell.2020.00147/fullischemia-reperfusionacute kidney injuryFGF2apoptosisER stress |
| spellingShingle | Xiaohua Tan Qianyu Tao Qianyu Tao Guixiu Li Lijun Xiang Xiaomeng Zheng Xiaomeng Zheng Tianzhen Zhang Cuijiao Wu Dequan Li Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress Frontiers in Cell and Developmental Biology ischemia-reperfusion acute kidney injury FGF2 apoptosis ER stress |
| title | Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress |
| title_full | Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress |
| title_fullStr | Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress |
| title_full_unstemmed | Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress |
| title_short | Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress |
| title_sort | fibroblast growth factor 2 attenuates renal ischemia reperfusion injury via inhibition of endoplasmic reticulum stress |
| topic | ischemia-reperfusion acute kidney injury FGF2 apoptosis ER stress |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00147/full |
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