Document Detail

Insulin-like growth factor-II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse.
MedLine Citation:
PMID:  23299523     Owner:  NLM     Status:  MEDLINE    
Podocytes are crucial for preventing the passage of albumin into the urine and, when lost, are associated with the development of albuminuria, renal failure and cardiovascular disease. Podocytes have limited capacity to regenerate, therefore pro-survival mechanisms are critically important. Insulin-like growth factor-II (IGF-II) is a potent survival and growth factor; however, its major function is thought to be in prenatal development, when circulating levels are high. IGF-II has only previously been reported to continue to be expressed in discrete regions of the brain into adulthood in rodents, with systemic levels being undetectable. Using conditionally immortalized human and ex vivo adult mouse cells of the glomerulus, we demonstrated the podocyte to be the major glomerular source and target of IGF-II; it signals to this cell via the IGF-I receptor via the PI3 kinase and MAPK pathways. Functionally, a reduction in IGF signalling causes podocyte cell death in vitro and glomerular disease in vivo in an aged IGF-II transgenic mouse that produces approximately 60% of IGF-II due to a lack of the P2 promoter of this gene. Collectively, this work reveals the fundamental importance of IGF-II in the mature podocyte for glomerular health across mammalian species.
L J Hale; G I Welsh; C M Perks; J A Hurcombe; S Moore; I Hers; M A Saleem; P W Mathieson; A J Murphy; M Jeansson; J M Holly; S N Hardouin; R J Coward
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-21
Journal Detail:
Title:  The Journal of pathology     Volume:  230     ISSN:  1096-9896     ISO Abbreviation:  J. Pathol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-11     Completed Date:  2013-06-13     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  95-106     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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MeSH Terms
Aging / physiology
Cell Line, Transformed
Cell Survival / physiology
Insulin-Like Growth Factor I / genetics,  metabolism
Insulin-Like Growth Factor II / genetics,  metabolism*
Kidney Glomerulus / cytology,  physiology
Mesangial Cells / cytology,  metabolism
Mice, Transgenic
Podocytes / cytology*,  metabolism*
RNA, Small Interfering / genetics
Signal Transduction / physiology*
Grant Support
G0501901//Medical Research Council; G0800200//Medical Research Council; PG/10/100/28658//British Heart Foundation; //Medical Research Council
Reg. No./Substance:
0/IGF2 protein, human; 0/IGF2 protein, mouse; 0/RNA, Small Interfering; 67763-96-6/Insulin-Like Growth Factor I; 67763-97-7/Insulin-Like Growth Factor II

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