Overexpression of cGMP-dependent protein kinase I (PKG-I) attenuates ischemia-reperfusion-induced kidney injury

Yanzhang Li, Xiaopeng Tong, Hasiyeti Maimaitiyiming, Kate Clemons, Ji Min Cao, Shuxia Wang

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish
Pages (from-to)F561-F570
JournalAmerican Journal of Physiology - Renal Physiology
Volume302
Issue number5
DOIs
StatePublished - Mar 2012

Funding

FundersFunder number
National Center for Research ResourcesP20RR021954

    Keywords

    • Apoptosis inflammation
    • Macrophage

    ASJC Scopus subject areas

    • Physiology
    • Urology

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