Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells.
Rebeca Fernandez-RuizAinhoa García-AlamánYaiza EstebanJoan Mir-CollBerta Serra-NavarroMarta Fontcuberta-PiSunyerChristophe BrocaMathieu ArmanetAnne WojtusciszynVardit KramMarian F YoungJosep VidalRamon GomisRosa GasaPublished in: Nature communications (2020)
Expanding the mass of pancreatic insulin-producing beta cells through re-activation of beta cell replication has been proposed as a therapy to prevent or delay the appearance of diabetes. Pancreatic beta cells exhibit an age-dependent decrease in their proliferative activity, partly related to changes in the systemic environment. Here we report the identification of CCN4/Wisp1 as a circulating factor more abundant in pre-weaning than in adult mice. We show that Wisp1 promotes endogenous and transplanted adult beta cell proliferation in vivo. We validate these findings using isolated mouse and human islets and find that the beta cell trophic effect of Wisp1 is dependent on Akt signaling. In summary, our study reveals the role of Wisp1 as an inducer of beta cell replication, supporting the idea that the use of young blood factors may be a useful strategy to expand adult beta cell mass.
Keyphrases
- induced apoptosis
- single cell
- cell proliferation
- cell therapy
- type diabetes
- endothelial cells
- cell cycle arrest
- cardiovascular disease
- stem cells
- cell death
- metabolic syndrome
- mesenchymal stem cells
- childhood cancer
- mechanical ventilation
- acute respiratory distress syndrome
- high fat diet induced
- bioinformatics analysis