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Departments of Cell Biology and Molecular Medicine (Y.-Q.Z., H.Z., A.M., H.K., T.T., I.K.), Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan; and Department of Internal Medicine and Molecular Science (J.-i.M.), Graduate School of Medicine, Osaka University, Suita 565-0871, Japan
Address all correspondence and requests for reprints to: Itaru Kojima, M.D., Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan. E-mail: ikojima{at}showa.gunma-u.ac.jp.
Activins expressed in progenitor cells of the pancreas regulate differentiation of endocrine cells during development. Neogenesis of ß-cells takes place in adult animals under some conditions, and ß-cells are thought to arise from precursors locating in the pancreatic duct. In the present study, we investigated whether or not activins are expressed in the duct where ß-cell neogenesis is initiated. mRNA for the ßA- and ßB-subunits was expressed in isolated mouse pancreatic ducts. Immunohistochemically, the ßA-subunit was detected in the pancreatic duct and colocalized with cytokeratin, a marker of ductal cells. The ßA-subunit was also expressed in nestin-positive cells in the duct. Likewise, the ßB-subunit was detected in the pancreatic duct. In addition, mRNA for the type II and type IIB activin receptors was expressed in the duct. Expression of mRNA for two activin subunits was markedly increased after streptozotocin injection. Similarly, the mRNA expression was up-regulated after partial pancreatectomy. These results indicate that activins are expressed in the pancreatic duct and are up-regulated shortly after the reduction of the ß-cell mass. Induction of activins in the duct may be a critical step in the initiation of ß-cell neogenesis.
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