Proximal tubule overexpression of a locally acting IGF isoform, Igf-1Ea, increases inflammation after ischemic injury

Rae, Fiona K., Suhaimi, Norseha, Li, Joan, Nastasi, Tommaso, Slonimsky, Esfir, Rosenthal, Nadia and Little, Melissa H. (2012) Proximal tubule overexpression of a locally acting IGF isoform, Igf-1Ea, increases inflammation after ischemic injury. Growth Hormone and IGF Research, 22 1: 6-16. doi:10.1016/j.ghir.2011.11.002

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Author Rae, Fiona K.
Suhaimi, Norseha
Li, Joan
Nastasi, Tommaso
Slonimsky, Esfir
Rosenthal, Nadia
Little, Melissa H.
Title Proximal tubule overexpression of a locally acting IGF isoform, Igf-1Ea, increases inflammation after ischemic injury
Formatted title
Proximal tubule overexpression of a locally acting IGF isoform, Igf-1Ea, increases inflammation after ischemic injury
Journal name Growth Hormone and IGF Research   Check publisher's open access policy
ISSN 1096-6374
1532-2238
Publication date 2012-02
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.ghir.2011.11.002
Volume 22
Issue 1
Start page 6
End page 16
Total pages 11
Place of publication Kidlington, U.K.
Publisher Churchill Livingstone
Collection year 2012
Language eng
Formatted abstract
Objective: IGF-1 is an important regulator of postnatal growth in mammals. In mice, a non-circulating, locally acting isoform of IGF-1, IGF-1Ea, has been documented as a central regulator of muscle regeneration and has been shown to improve repair in the heart and skin. In this study, we examine whether local production of IGF1-Ea protein improves tubular repair after renal ischemia reperfusion injury.

Design: Transgenic mice in which the proximal-tubule specific promoter Sglt2 was driving the expression of an Igf-1Ea transgene. These animals were treated with an ischemic-reperfusion injury and the response at 24 h and 5 days compared with wildtype littermates.

Results: Transgenic mice demonstrated rapid and enhanced renal injury in comparison to wild type mice. Five days after injury the wild type and low expressing Igf-1Ea transgenic mice showed significant tubular recovery, while high expressing Igf-1Ea transgenic mice displayed significant tubular damage. This marked injury was accompanied by a two-fold increase in the number of F4/80 positive macrophages and a three-fold increase in the number of Gr1-positive neutrophils in the kidney. At the molecular level, Igf-1Ea expression resulted in significant up-regulation of proinflammatory cytokines such as TNF-α and Ccl2. Expression of Nfatc1 was also delayed, suggesting reduced tubular proliferation after kidney injury.

Conclusions: These data indicate that, unlike the muscle, heart and skin, elevated levels of IGF-1Ea in the proximal tubules exacerbates ischemia reperfusion injury resulting in increased recruitment of macrophages and neutrophils and delays repair in a renal setting.
Keyword Igf-1Ea
IGF-1Ea
Kidney
Ischemia reperfusion injury
Acute kidney injury
Macrophages
Neutrophils
Proximal tubules
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 23 December 2011.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 03 Jan 2012, 10:06:42 EST by Joan Li on behalf of Institute for Molecular Bioscience