title: Cathelicidin PR-39 peptide inhibits hypoxia/reperfusion-induced kidney cell apoptosis by suppression of the endoplasmic reticulum-stress pathway.
abstract: Ischemia/reperfusion injury (IRI) is a major cause of acute kidney damage, which often occurs in deceased donor kidney transplants. Cathelicidin PR-39 peptide possesses anti-inflammatory and wound repair effects through tissue angiogenesis and anti-apoptosis. This study assessed the role of PR-39 in anti-apoptosis in vitro using a lentiviral vector with a kidney specific promoter (KSP) to drive PR-39 expression. Our data revealed that PR-39 peptide was specifically over-expressed in kidney-derived HK-2 cells, but was scarcely detected in non-kidney tissue-derived cells. PR-39 over-expression had a protective role in the hypoxia/re-oxygenation (H/R) treated cells. The anti-apoptotic activity of PR-39 peptide was mediated by the inhibition of caspase-2, caspase-12 and caspase-3 activity in the endoplasmic reticulum (ER) stress-induced apoptotic pathway. It was also revealed that the anti-apoptotic effect of PR-39 peptide was mediated by an apoptosis-related protein, cellular inhibitor apoptosis protein-2 (c-IAP-2). Taken together, the current data demonstrate that PR-39 expression driven by KSP could prevent kidney damage (apoptosis) from IRI via the ER stress-induced apoptotic pathway.
authors.affiliation: Department of Kidney Transplant, Hospital of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Kidney Transplant, Hospital of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China xwujun@126.com helixiang@163.com.
authors.forename: Wujun
authors.initials: W
authors.lastname: Xue
authors.affiliation: Department of Kidney Transplant, Hospital of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China xwujun@126.com helixiang@163.com.
authors.forename: Heli
authors.initials: H
authors.lastname: Xiang
authors.affiliation: Department of Kidney Transplant, Hospital of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Kidney Transplant, Hospital of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Kidney Transplant, Hospital of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Lizi
authors.initials: L
authors.lastname: Jiao
authors.affiliation: Department of Kidney Transplant, Hospital of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Zizhao
authors.initials: Z
authors.lastname: Jiao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D054804:Cathelicidins / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D000860:Hypoxia / Q000517:prevention & control*; D007668:Kidney / Q000473:pathology; D051379:Mice; D041681:NIH 3T3 Cells; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*
chemical_list: D054804:Cathelicidins
keywords: PR-39; anti-apoptosis; ischemia/reperfusion injury; kidney specific promoter (KSP); kidney-derived HK-2 cells