Bcl-2 Protects Tubular Epithelial Cells from Ischemia Reperfusion Injury by Inhibiting Apoptosis
Ischemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered to be the most important cause of graft dysfunction in kidney transplantation subjected to ischemia. The mechanism that triggers inflammation and renal injury after ischemia remains to be elucid...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2008-01-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/000000008783907053 |
| _version_ | 1818504684140232704 |
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| author | Chigure Suzuki Yoshitaka Isaka Shigeomi Shimizu Yoshihide Tsujimoto Yoshitsugu Takabatake Takahito Ito Shiro Takahara Enyu Imai |
| author_facet | Chigure Suzuki Yoshitaka Isaka Shigeomi Shimizu Yoshihide Tsujimoto Yoshitsugu Takabatake Takahito Ito Shiro Takahara Enyu Imai |
| author_sort | Chigure Suzuki |
| collection | DOAJ |
| description | Ischemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered to be the most important cause of graft dysfunction in kidney transplantation subjected to ischemia. The mechanism that triggers inflammation and renal injury after ischemia remains to be elucidated; however, cellular stress may induce apoptosis during the first hours and days after transplantation, which might play a crucial role in early graft dysfunction. Bcl-2 is known to inhibit apoptosis induced by the etiological factors promoting ischemia and reperfusion injury. Accordingly, we hypothesized that an augmentation of the antiapoptotic factor Bcl-2 may thus protect tubular epithelial cells by inhibiting apoptosis, thereby ameliorating the subsequent tubulointerstitial injury. We examined the effects of Bcl-2 overexpression on ischemia-reperfusion (I/R) injury using Bcl-2 transgenic mice (Bcl-2 TG) and their wild-type littermates (WT). To investigate the effects of I/R injury, the left renal artery and vein were clamped for 45 min, followed by reperfusion for 0–96 h. Bcl-2 TG exhibited decreased active caspase protein in the tubular cells, which led to a reduction in TUNEL-positive apoptotic cells. Consequently, interstitial fibrosis and phenotypic changes were ameliorated in Bcl-2 TG. In conclusion, Bcl-2 augmentation protected renal tubular epithelial cells from I/R, and subsequent interstitial injury by inhibiting tubular apoptosis. |
| first_indexed | 2024-12-10T21:40:26Z |
| format | Article |
| id | doaj.art-0a9efbc146754800ab88dc079bd83b2e |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-10T21:40:26Z |
| publishDate | 2008-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-0a9efbc146754800ab88dc079bd83b2e2022-12-22T01:32:31ZengSAGE PublishingCell Transplantation0963-68971555-38922008-01-011710.3727/000000008783907053Bcl-2 Protects Tubular Epithelial Cells from Ischemia Reperfusion Injury by Inhibiting ApoptosisChigure Suzuki0Yoshitaka Isaka1Shigeomi Shimizu2Yoshihide Tsujimoto3Yoshitsugu Takabatake4Takahito Ito5Shiro Takahara6Enyu Imai7Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Post-Genomics & Diseases, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Post-Genomics & Diseases, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, JapanIschemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered to be the most important cause of graft dysfunction in kidney transplantation subjected to ischemia. The mechanism that triggers inflammation and renal injury after ischemia remains to be elucidated; however, cellular stress may induce apoptosis during the first hours and days after transplantation, which might play a crucial role in early graft dysfunction. Bcl-2 is known to inhibit apoptosis induced by the etiological factors promoting ischemia and reperfusion injury. Accordingly, we hypothesized that an augmentation of the antiapoptotic factor Bcl-2 may thus protect tubular epithelial cells by inhibiting apoptosis, thereby ameliorating the subsequent tubulointerstitial injury. We examined the effects of Bcl-2 overexpression on ischemia-reperfusion (I/R) injury using Bcl-2 transgenic mice (Bcl-2 TG) and their wild-type littermates (WT). To investigate the effects of I/R injury, the left renal artery and vein were clamped for 45 min, followed by reperfusion for 0–96 h. Bcl-2 TG exhibited decreased active caspase protein in the tubular cells, which led to a reduction in TUNEL-positive apoptotic cells. Consequently, interstitial fibrosis and phenotypic changes were ameliorated in Bcl-2 TG. In conclusion, Bcl-2 augmentation protected renal tubular epithelial cells from I/R, and subsequent interstitial injury by inhibiting tubular apoptosis.https://doi.org/10.3727/000000008783907053 |
| spellingShingle | Chigure Suzuki Yoshitaka Isaka Shigeomi Shimizu Yoshihide Tsujimoto Yoshitsugu Takabatake Takahito Ito Shiro Takahara Enyu Imai Bcl-2 Protects Tubular Epithelial Cells from Ischemia Reperfusion Injury by Inhibiting Apoptosis Cell Transplantation |
| title | Bcl-2 Protects Tubular Epithelial Cells from Ischemia Reperfusion Injury by Inhibiting Apoptosis |
| title_full | Bcl-2 Protects Tubular Epithelial Cells from Ischemia Reperfusion Injury by Inhibiting Apoptosis |
| title_fullStr | Bcl-2 Protects Tubular Epithelial Cells from Ischemia Reperfusion Injury by Inhibiting Apoptosis |
| title_full_unstemmed | Bcl-2 Protects Tubular Epithelial Cells from Ischemia Reperfusion Injury by Inhibiting Apoptosis |
| title_short | Bcl-2 Protects Tubular Epithelial Cells from Ischemia Reperfusion Injury by Inhibiting Apoptosis |
| title_sort | bcl 2 protects tubular epithelial cells from ischemia reperfusion injury by inhibiting apoptosis |
| url | https://doi.org/10.3727/000000008783907053 |
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