Research on Effects of Cadmium Induced Intestinal Epithelial Cell Injury and Regulation on Intestinal Stem Cells Regeneration and Differentiation in Drosophila Mid-gut

Abstract: Cadmium is a typical toxic heavy metal element， which is extremely harmful for people’s health in environment. To explore the harmful mechanism of cadmium in digestive system， we use the Drosophila adult mid-gut， which is proved an excellent model to study tissue damage and intestinal stem cell (ISC) regulation mechanisms. In this work， the flies were fed with different concentrations of cadmium chloride. Cadmium over intake could induce ultra-structural damage in mid-gut epithelial cells， especially the nuclear membrane， mitochondrion and microvilli. The level of damage is directly depending on the concentrations of cadmium used. Immunofluorescence studies show that the number and proportion of ISC， enteroblast (EB)， enterocyte (EC) are varied among different cadmium feeding groups， as cadmium could up-regulate the proliferation and differentiation ability of ISC. Real-time RT-PCR data demonstrate that cadmium treatment induces over-expression of epidermal growth factor receptor (EGFR) and JAK/STAT ligands in fly guts. All our results demonstrated that mid-gut epithelial cell damaged by cadmium treatments were mainly manifested by nuclear membrane blurring or wrinkle， mitochondrial swelling， vacuolization， hetero-pyknosis and intestinal microvilli defects. And the ultra-structural damaged in Ecs could up-regulate the expression of EGFR and JAK/STAT signaling ligands， which promoted ISC proliferation and differentiation. Thus the gut regenerates through refurnishing the damaged ECs by newly differentiated cells from ISCs. So， this mechanism enables digestive system to adapt the toxic environmental heavy metals， like cadmium.However， overactivation of these signaling pathways could also lead to potential tumorigenesis in gut.

CSTR: 32200.14.cjcb.2013.05.0007