Expression and possible role of IGF-IR in the mouse gastric myenteric plexus and smooth muscles

Abstract

Insulin-like growth factor-I (IGF-I) and its receptor (IGF-IR) have tremendous trophic effects on the central, peripheral and enteric neurons. The loss of IGF-IR contributes to the development of diabetic gastroparesis. However, the nature and the function of the IGF-IR+ cells in the gastric myenteric plexus remain unclear. In this study, anti-ChAT, anti-S100β or anti-c-KIT antibodies were used to co-label IGF-IR+ cells and neurons, glial cells or interstitial cells of Cajal (ICCs), respectively. We also generated type 1 diabetic mice (DM) to explore the influence of impaired IGF-I/IGF-IR in the myenteric neurons. Results showed that IGF-IR was expressed in the epithelium, smooth muscles and myenteric plexi of the mouse stomach. Most of the IGF-IR+ cells in the myenteric plexi were ChAT+ cholinergic neurons, but not enteric glial cells and there were more IGF-IR+ neurons and fibers in the gastric antrum than in the corpus. The IGF-IR+/ChAT+ neurons and ICCs were closely juxtaposed, but distinctly distributed in the myenteric plexus, indicating a possible role for the IGF-IR+/ChAT+ neurons in the mediation of gastric motility through ICCs. Moreover, the decrease of IGF-IR and cholinergic neurons in the myenteric plexi and smooth muscles of DM mice suggested that IGF-I/IGF-IR signaling might play a role in neuron survival and neurite outgrowth, as well as stem cell factor (SCF) production, which is required for the development of ICCs. Our results provide insights into the effects of IGF-I/IGF-IR signaling on the development of gastrointestinal motility disorders.