Molecular and histopathological profiling of imiquimod induced dermatosis in Swiss Wistar rats: contribution to the rat model for novel anti-psoriasis treatments

Molecular Biology Reports - Imiquimod (IMQ) induced human-like psoriasis in mice has been shown to be effective in testing and development of novel treatments. The IMQ psoriasis model has become...     

ActivinB Is Induced in Insulinoma To Promote Tumor Plasticity through a β-Cell-Induced Dedifferentiation

Loss of pancreatic β-cell maturity occurs in diabetes and insulinomas. Although both physiological and pathological stresses are known to promote β-cell dedifferentiation, little is known about the molecules involved in this process. Here we demonstrate that activinB, a transforming growth factor β (TGF-β)-related ligand, is upregulated during tumorigenesis and drives the loss of insulin expression and β-cell maturity in a mouse insulinoma model. Our data further identify Pax4 as a previously unknown activinB target and potent contributor to the observed β-cell dedifferentiation. More importantly, using compound mutant mice, we found that deleting activinB expression abolishes tumor β-cell dedifferentiation and, surprisingly, increases survival without significantly affecting tumor growth. Hence, this work reveals an unexpected role for activinB in the loss of β-cell maturity, islet plasticity, and progression of insulinoma through its participation in β-cell dedifferentiation.