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Aims/hypothesis We previously reported that exposure to antibodies neutralising serpin B13, a protease inhibitor expressed in exocrine pancreatic ducts, promotes beta cell proliferation, underscoring the importance of a functional relationship between exocrine and endocrine pancreas. The aim of the present study was to identify the molecular events that link inhibition of serpin B13 to islet cell proliferation. Methods We used an in vitro culture system consisting of isolated pancreatic islets, an extract of pancreatic ductal epithelium and a monoclonal antibody (mAb) to serpin B13 or IgG isotype control. In vivo studies involved treatment of mice with these mAbs. Results The catalytic activity of cathepsin L (CatL), a cysteine protease target of serpin B13, was augmented in the pancreas of mice injected with serpin B13 mAb. Furthermore, the addition of serpin B13 mAb to the islets, together with the pancreatic ductal epithelium lysate, caused CatL-dependent cleavage of E-cadherin and concomitant upregulation of REG genes, ultimately leading to beta cell proliferation. Direct blockade of E-cadherin with mAb also markedly enhanced REG gene induction, while chemical inhibition of β-catenin, a binding target of E-cadherin, prevented the serpin B13 mAb-induced upregulation of REG genes. Conclusions/interpretation Our work implicates the CatL-E-cadherin-REG pathway in the regulation of islet cell proliferation in response to signals generated in exocrine pancreatic tissue and demonstrates that protease activity may promote adaptive changes in the islets. Data availability Microarray data that support the findings of this study have been deposited in Gene Expression Omnibus (GEO) with the accession no. GSE125151.

In the fabrication of plastic components with micro or nano structures, injection molding is one of the simple and most cost-effective processes. In the injection molding process, a complete filling of the micro or nano structures is necessary to fabricate a successful product. However, it is difficult to fully fill nano structures with an aspect ratio close to one or higher by the conventional molding process. In this study, mold inserts with nano channels were constructed by a LIGA-like process. The effects of the processing parameters and infrared heating on the filling of the nano structures were explored experimentally. Increasing the mold temperature, pressure, or filling rate did not improve the filling distance in nano channels with the conventional molding process significantly. Thus, an infrared mold surface heating system was introduced to assist the molding of the nano structures. To enhance the heating efficiency and reduce the cycle time, a heat-resistant layer was inserted under the mold cavity. The heat resistant plate led the heating system to work more efficiently. It easily increased the surface temperature over the glass transition temperature of plastic, thus fully filling the nano structures.

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