Research Of TGFR-Ⅱ During The Later Development Of The Pancreas

Diabetes mellitus(DM) is a disorder of glucose homeostasis, either due to the immune-mediated eradication of pancreatic beta cells in the islets of Langerhans (type 1 diabetes) or resulting from insulin resistance and obesity syndromes where the insulin-producing capability of the beta cell is ultimately exhausted in the face of insensitivity to the effects of insulin in the peripheral glucose-utilising tissues (type 2 diabetes). This disease has been regarded as one of the most serious disease of human.beta-cell replacement therapy via islet transplantation offers today important perspectives for the treatment of type 1 diabetes. But the problems of donor tissue shortage and implant rejection are two problems which must be overcome. The recent discovery of heretofore unknown, multipotential stem cells within the embryonic and adult islets of Langerhans and embryonic stem (ES) cells suggests new therapeutic options for the treatment of diabetes mellitus type 1 because of the capacity of stem cells for virtually unlimited self-renewal and differentiation.One of the most common strategies to induce in-vitro differentiation of stem cell is to add extracellular signals, such as growth factors. The purpose of our research is to search the growth factors which induce in-vitro differentiation of pancreatic stem cell to pancreatic beta-cell which synthesize and secrete insulin respond to the stimulation of glucose. Transforming growth factor-beta 1 (TGF- β 1) is known to regulate cell growth, differentiation, and function in developing mammalian systems. Altering TGF-β 1 expression in the developing pancreas has been shown to affect both exocrine and endocrine development, suggesting that it is an important regulator of pancreatic organogenesis. And so, it maybe a important regulator of the differentiation of pancreatic stem cell. Our work focus on the expression of TGF- β 1 and its receptors.TGF-beta binds specifically and with high affinity to all cell types with few exceptions. There are at least nine types of cell surface proteins that specifically bind TGF-beta. The most abundant and largest of the cell surface TGF-beta binding proteins is a membrane-bound proteoglycan that is a dimer of subunits each with Mr of approximately 250,000 (beta-glycan). It does not appear to be associated with TGF-beta-mediated cell responses and its function is regulating the affinity between receptor and ligand as well as the expression of type II. TGF-beta-induced responses appear to be mediated by type I and type II receptor which have an Mr of approximately 50,000 and approximately 80,000, respectively. . Primary binding of the ligand occurs with the RII receptor, promoting formation of a heterodimer with RI and activation of signaling.We performed Western blot for T β RII on pancreas protein obtained from SD rats on gestational days 18.5 (E18.5), 21 (E21), and adult. We also isolated mRNA from the pancreas on each of these days and performed a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to assess relative T β RII expression as a function of gestational age.