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Article: Insulin-like growth factor-II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse

TitleInsulin-like growth factor-II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse
Authors
Issue Date2013
Citation
Journal of Pathology, 2013, v. 230 n. 1, p. 95-106 How to Cite?
AbstractPodocytes 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. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/195404
ISSN
2015 Impact Factor: 7.381
2015 SCImago Journal Rankings: 4.176
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHale, LJ-
dc.contributor.authorWelsh, GI-
dc.contributor.authorPerks, CM-
dc.contributor.authorHurcombe, JA-
dc.contributor.authorMoore, S-
dc.contributor.authorHers, I-
dc.contributor.authorSaleem, MA-
dc.contributor.authorMathieson, PW-
dc.contributor.authorMurphy, AJ-
dc.contributor.authorJeansson, M-
dc.contributor.authorHolly, JM-
dc.contributor.authorHardouin, SN-
dc.contributor.authorCoward, RJ-
dc.date.accessioned2014-02-28T06:12:06Z-
dc.date.available2014-02-28T06:12:06Z-
dc.date.issued2013-
dc.identifier.citationJournal of Pathology, 2013, v. 230 n. 1, p. 95-106-
dc.identifier.issn0022-3417-
dc.identifier.urihttp://hdl.handle.net/10722/195404-
dc.description.abstractPodocytes 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. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.-
dc.languageeng-
dc.relation.ispartofJournal of Pathology-
dc.titleInsulin-like growth factor-II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/path.4165-
dc.identifier.pmid23299523-
dc.identifier.scopuseid_2-s2.0-84876138192-
dc.identifier.volume230-
dc.identifier.issue1-
dc.identifier.spage95-
dc.identifier.epage106-
dc.identifier.isiWOS:000317434000011-

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