Abstract
Insulin receptor substrate (IRS) proteins play a central role in insulin signaling. Previously we have demonstrated that insulin is essential for normal skin development and function. In the present study we investigated the involvement of the IRSβ1 and IRSβ2 proteins in skin physiology and in mediating insulin action in skin. For this purpose we have investigated the effects of inactivation of each of the IRSs on skin, studying skin sections and primary skin cells derived from IRSβ1 or IRSβ2 null mice. We have demonstrated that while the skin of the IRSβ2 null mice appeared normal, the skin of the IRSβ1 null mice was thinner and translucent. Histological analysis revealed that the thinning of the IRSβ1 null skin was a consequence of the thinning of the spinous compartment, consisting of fewer layers. Proliferation of the IRSβ1 and IRSβ2 null skin epidermal cells was normal. However, the differentiation process of the IRSβ1 skin and skin cells was impaired. There was a marked decrease in the induction of the expression of K1, the marker of advanced stages of skin differentiation. In contrary, IRSβ2 inactivation had no effects on skin differentiation. In conclusion, we have shown for the first time that IRSβ1 but not IRSβ2 has an effect on skin formation and development, being one of the main activators of the differentiation process in skin keratinocytes. Furthermore, we suggest that IRSβ1 and IRSβ2 have distinct roles in skin physiology. J. Cell. Physiol. 213: 519β527, 2007. Β© 2007 WileyβLiss, Inc.