title: Bcl-2 protects tubular epithelial cells from ischemia reperfusion injury by inhibiting apoptosis.
abstract: 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.
authors.affiliation: Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Chigure
authors.initials: C
authors.lastname: Suzuki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
authors.forename: Shigeomi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Tsujimoto
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Takabatake
authors.forename: Takahito
authors.initials: T
authors.lastname: Ito
authors.forename: Shiro
authors.initials: S
authors.lastname: Takahara
authors.forename: Enyu
authors.initials: E
authors.lastname: Imai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D019254:Genes, bcl-2; D006801:Humans; D007668:Kidney / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D007686:Kidney Tubules, Distal / Q000473:pathology / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012079:Renal Circulation / Q000235:genetics; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2