Transfer of growth factor receptor mRNA via exosomes unravels the regenerative effect of mesenchymal stem cells.
Bone marrow-mesenchymal stem cells (BM-MSC) ameliorate renal dysfunction and repair tubular damage of acute kidney injury by locally releasing growth factors, including the insulin-like growth factor-1 (IGF-1). The restricted homing of BM-MSC at the site of injury led us to investigate a possible gene-based communication mechanism between BM-MSC and tubular cells. Human BM-MSC (hBM-MSC) released microparticles and exosomes (Exo) enriched in mRNAs. A selected pattern of transcripts was detected in Exo versus parental cells. Exo expressed the IGF-1 receptor (IGF-1R), but not IGF-1 mRNA, while hBM-MSC contained both mRNAs. R- cells lacking IGF-1R exposed to hBM-MSC-derived Exo acquired the human IGF-1R transcript that was translated in the corresponding protein. Transfer of IGF-1R mRNA from Exo to cisplatin-damaged proximal tubular cells (proximal tubular epithelial cell [PTEC]) increased PTEC proliferation. Coincubation of damaged PTEC with Exo and soluble IGF-1 further enhanced cell proliferation. These findings suggest that horizontal transfer of the mRNA for IGF-1R to tubular cells through Exo potentiates tubular cell sensitivity to locally produced IGF-1 providing a new mechanism underlying the powerful renoprotection of few BM-MSC observed in vivo.
Mario Negri Institute for Pharmacological Research, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy. susanna.tomasoni@marionegri.it
Susanna
S
Tomasoni
Lorena
L
Longaretti
Cinzia
C
Rota
Marina
M
Morigi
Sara
S
Conti
Elisa
E
Gotti
Chiara
C
Capelli
Martino
M
Introna
Giuseppe
G
Remuzzi
Ariela
A
Benigni
D058186:Acute Kidney Injury / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002450:Cell Communication; D049109:Cell Proliferation; D002478:Cells, Cultured; D055354:Exosomes; D022761:Gene Transfer, Horizontal; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering; D017978:Receptors, Growth Factor / Q000235:genetics*
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017978:Receptors, Growth Factor; D007334:Insulin-Like Growth Factor I