Heterozygosity for Fibrinogen Results in Efficient Resolution of Kidney Ischemia Reperfusion Injury

View/ Open
Published Version
https://doi.org/10.1371/journal.pone.0045628Metadata
Show full item recordCitation
Ajay, Amrendra Kumar, Janani Saikumar, Vanesa Bijol, and Vishal S. Vaidya. 2012. Heterozygosity for fibrinogen results in efficient resolution of kidney ischemia reperfusion injury. PLoS ONE 7(9): e45628.Abstract
Fibrinogen (Fg) has been recognized to play a central role in coagulation, inflammation and tissue regeneration. Several studies have used Fg deficient mice (Fg−/−) in comparison with heterozygous mice (Fg+/−) to point the proinflammatory role of Fg in diverse pathological conditions and disease states. Although Fg+/− mice are considered ‘normal’, plasma Fg is reduced to ∼75% of the normal circulating levels present in wild type mice (Fg+/+). We report that this reduction in Fg protein production in the Fg+/− mice is enough to protect them from kidney ischemia reperfusion injury (IRI) as assessed by tubular injury, kidney dysfunction, necrosis, apoptosis and inflammatory immune cell infiltration. Mechanistically, we observed binding of Fg to ICAM-1 in kidney tissues of Fg+/+ mice at 24 h following IRI as compared to a complete absence of binding observed in the Fg+/− and Fg−/− mice. Raf-1 and ERK were highly activated as evident by significantly higher phosphorylation in the Fg+/+ kidneys at 24 h following IRI as compared to Fg+/− and Fg−/− mice kidneys. On the other hand Cyclin D1 and pRb, indicating higher cell proliferation, were significantly increased in the Fg+/− and Fg−/− as compared to Fg+/+ kidneys. These data suggest that Fg heterozygosity allows maintenance of a critical balance of Fg that enables regression of initial injury and promotes faster resolution of kidney damage.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446934/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:10579125
Collections
- HMS Scholarly Articles [17298]
- SPH Scholarly Articles [6269]
Contact administrator regarding this item (to report mistakes or request changes)