Τίτλος:
Effect of Heme Oxygenase-1 Deficiency on Glomerular Proteomics
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: The cytoprotective effect of heme oxygenase (HO)-1 in various forms of renal glomerular injury is established. However, little is known on the role of HO-1 in preserving glomerular structural/functional integrity in the absence of injury. The present study addressed this question in HO-1-deficient rats. Methods: HO-1-deficient rats were generated using zinc finger nuclease-mediated HO-1 gene ( Hmox1 ) disruption and studied. Glomeruli were isolated from HO-1-deficient ( Hmox1 -/- ) rats and their wild type (WT) littermates for proteomic analysis. Results: Glomerular lesions were characterized and differentially expressed proteins important for preserving integrity of the glomerular filtration barrier were identified. HO-1-deficient ( Hmox1 -/- ) rats developed albuminuria with decreased glomerular filtration rate. In albuminuric rats, there were lesions resembling focal and segmental glomerulosclerosis (FSGS). Western blot analysis of the integral slit diaphragm proteins, nephrin and podocin revealed a significant decrease in nephrin, with no change in podocin. Proteomic analysis of glomerular protein lysates from Hmox1 -/- and WT rats revealed differential expression of proteins previously linked with FSGS pathogenesis. Specifically, ?-actinin-4, actin related protein 3, cytokeratins and novel candidates including transgelin-2 and lamins. Bioinformatic analysis predicted the upregulation of pathways implicated in platelet aggregation and fibrin clot formation. Conclusion: HO-1 is a putative regulator of proteins important in preserving glomerular structural stability and integrity, and in minimizing the activity of proinflammatory pathways. © 2016 S. Karger AG, Basel.
Συγγραφείς:
Detsika, M.G.
Lygirou, V.
Frantzis, V.
Zoidakis, J.
Atsaves, V.
Poulaki, E.
Gakiopoulou, H.
Vlahou, A.
Lianos, E.A.
Περιοδικό:
American Journal of Nephrology
Λέξεις-κλειδιά:
aconitate hydratase; actin related protein 3; adenosine triphosphatase; aldehyde reductase; alpha actinin 4; aspartate aminotransferase isoenzyme 2; creatinine; cytokeratin; cytoskeleton protein; elongation factor Tu; fibrinogen; glucose regulated protein 94; glycerophosphoinositol inositolphosphodiesterase; glycine amidinotransferase; heme oxygenase 1; hemopexin; keratin type I; keratin type II; lamin A; lamin C; nephrin; peptidylprolyl isomerase; podocin; protein disulfide isomerase; proteome; proton transporting adenosine triphosphate synthase; transgelin; transgelin 2; unclassified drug; voltage dependent anion channel 1; heme oxygenase 1; proteome, albuminuria; animal experiment; animal model; animal tissue; Article; bioinformatics; citric acid cycle; controlled study; creatinine blood level; creatinine urine level; fibrin clot; focal glomerulosclerosis; glomerular filtration barrier; glomerulopathy; glomerulus filtration rate; male; molecular weight; nonhuman; nuclear lamina; nuclear pore; phenotype; priority journal; protein analysis; protein expression; protein urine level; proteomics; rat; thrombocyte aggregation; upregulation; Western blotting; animal; deficiency; glomerulus; growth disorder; hemolytic anemia; iron metabolism disorder; metabolism; pathology; Sprague Dawley rat, Anemia, Hemolytic; Animals; Growth Disorders; Heme Oxygenase-1; Iron Metabolism Disorders; Kidney Glomerulus; Male; Proteome; Rats, Sprague-Dawley
