title: Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury.
abstract: cGMP-dependent protein kinase (PKG) is a multifunctional protein. Whether PKG plays a role in ischemia-reperfusion-induced kidney injury (IRI) is unknown. In this study, using an in vivo mouse model of renal IRI, we determined the effect of renal IRI on kidney PKG-I levels and also evaluated whether overexpression of PKG-I attenuates renal IRI. Our studies demonstrated that PKG-I levels (mRNA and protein) were significantly decreased in the kidney from mice undergoing renal IRI. Moreover, PKG-I transgenic mice had less renal IRI, showing improved renal function and less tubular damage compared with their wild-type littermates. Transgenic mice in the renal IRI group had decreased tubular cell apoptosis accompanied by decreased caspase 3 levels/activity and increased Bcl-2 and Bag-1 levels. In addition, transgenic mice undergoing renal IRI demonstrated reduced macrophage infiltration into the kidney and reduced production of inflammatory cytokines. In vitro studies showed that peritoneal macrophages isolated from transgenic mice had decreased migration compared with control macrophages. Taken together, these results suggest that PKG-I protects against renal IRI, at least in part through inhibiting inflammatory cell infiltration into the kidney, reducing kidney inflammation, and inhibiting tubular cell apoptosis.
authors.affiliation: Graduate Center for Nutritional Sciences, Univ. of Kentucky, Lexington, KY 40536, USA.
authors.forename: Yanzhang
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Tong
authors.forename: Hasiyeti
authors.initials: H
authors.lastname: Maimaitiyiming
authors.forename: Kate
authors.initials: K
authors.lastname: Clemons
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Cao
authors.forename: Shuxia
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D017869:Cyclic GMP-Dependent Protein Kinases; D053148:Caspase 3