Clusterin, an intriguing biological regulator of the pancreas

초록

Clusterin, an intriguing biological regulator of the pancreas In-Sun Park Department of Anatomy and Center for Advanced Medical Education by BK21 project, School of Medicine, Inha University, Incheon 400-103, Korea. E-mail: sunpark@inha.ac.kr Insulin–producing beta cell of the pancreas is considered as a key target for current stem cell study and regenerative medicine. Clusterin is an intriguing glycoprotein expressed in association with a variety of patho-physiological conditions in various tissues including pancreas. We have illustrated clusterin function in pancreatic tissues, particularly regarding with the biological feature of insulin secreting beta cells. We have reported the transient expression of clusterin and its modification along with the islet cell development as well as its up-regulation upon cytotoxic insult of beta cells. Recently, we found that this protein is involved in regeneration of pancreatic endocrine cells following various types of tissue injuries and involved in the neogenic regeneration and reorganization of pancreatic tissue. Over-expression of clusterin induced a significant increase of beta cell differentiation, and deletion of secreted clusterin in the culture medium gave rise to a lazy transformation of insulin secreting cells from duct explants, implying a growth factor-like action of clusterin and its paracrine nature. Although mechanisms of clusterin action have not been defined, clusterin is known to be regulated by growth factors. Clusterin directly interacts with the intracellular segment of TGF-beta receptors inducing their phosphorylation. It implies that clusterin may rather function as a signaling molecule for inducing proliferation and differentiation with the help of growth factors. More recently, using clusterin transgenic (CLU+/+) and knock-out (CLU-/-), we confirmed cooperative action upon beta cell function and survival opposing diabetic condition. Based on these data, we can conclude that clusterin is an im