title: Insulin-like growth factor-1 sustains stem cell mediated renal repair.
abstract: In mice with cisplatin-induced acute kidney injury, administration of bone marrow-derived mesenchymal stem cells (MSC) restores renal tubular structure and improves renal function, but the underlying mechanism is unclear. Here, we examined the process of kidney cell repair in co-culture experiments with MSC and cisplatin-injured proximal tubular epithelial cells (PTEC). Exposure of PTEC to cisplatin markedly reduced cell viability at 4 days, but co-culture with MSC provided a protective effect by promoting tubular cell proliferation. This effect was mediated by insulin-like growth factor-1 (IGF-1), highly expressed by MSC as mRNA and protein, since blocking the growth factor's function with a specific antibody attenuated cell proliferation of PTEC. Confirming this, knocking down IGF-1 expression in MSC by small interfering-RNA also resulted in a significant decrease in PTEC proliferation and increased apoptosis. Furthermore, in the murine model of cisplatin-induced kidney injury, administering IGF-1 gene-silenced MSC limited their protective effect on renal function and tubular structure. These findings indicate that MSC exert beneficial effects on tubular cell repair in acute kidney injury by producing the mitogenic and pro-survival factor IGF-1.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Bergamo, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Imberti
authors.forename: Marina
authors.initials: M
authors.lastname: Morigi
authors.forename: Susanna
authors.initials: S
authors.lastname: Tomasoni
authors.forename: Cinzia
authors.initials: C
authors.lastname: Rota
authors.forename: Daniela
authors.initials: D
authors.lastname: Corna
authors.forename: Lorena
authors.initials: L
authors.lastname: Longaretti
authors.forename: Daniela
authors.initials: D
authors.lastname: Rottoli
authors.forename: Federica
authors.initials: F
authors.lastname: Valsecchi
authors.forename: Ariela
authors.initials: A
authors.lastname: Benigni
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.forename: Carla
authors.initials: C
authors.lastname: Zoja
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002945:Cisplatin; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007674:Kidney Diseases / Q000628:therapy*; D007687:Kidney Tubules, Proximal / Q000473:pathology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D007334:Insulin-Like Growth Factor I; D002945:Cisplatin