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

• DOI: 10.1002/path.4165
• Publication Date: 2013-01-09T01:17:21Z
• Authors: LJ Hale; GI Welsh; CM Perks; JA Hurcombe; S Moore; I Hers; MA Saleem; PW Mathieson; AJ Murphy; M Jeansson; JM Holly; SN Hardouin; RJ Coward
• Keywords: Albuminuria

Podocytes are crucial for preventing the passage of albumin into urine and, when lost, associated with development albuminuria, renal failure and cardiovascular disease. have limited capacity to regenerate, therefore pro-survival mechanisms critically important. Insulin-like growth factor-II (IGF-II) is a potent survival factor; however, its major function thought be in prenatal development, circulating levels high. IGF-II has only previously been reported continue expressed discrete regions brain adulthood rodents, systemic being undetectable. Using conditionally immortalized human ex vivo adult mouse cells glomerulus, we demonstrated podocyte glomerular source target IGF-II; it signals this cell via IGF-I receptor PI3 kinase MAPK pathways. Functionally, reduction IGF signalling causes death vitro disease an aged transgenic that produces approximately 60% due lack P2 promoter gene. Collectively, work reveals fundamental importance mature health across mammalian species.