Regulation of β-cell Proliferation by Antibody Response to Serpin B13
To examine the possibility that anti-serpin B13 antibody affects non-inflamed islets in alternative ways that are independent of the effects on autoimmunity we injected healthy Balb/c animals with serpin B13 mAb and discovered that these mice had increased numbers of pancreatic islets, increased beta cell mass and b cell proliferation, and upregulated expression of Reg genes that have been implicated in β cell renewal. We also found that adding serpin B13 mAb to the islets in vitro together with an extract of the pancreatic duct epithelium (in which serpin B13 is expressed) leads to significant upregulation of β-cell proliferation and expression of Reg genes. A similar treatment with an extract of non-ductal pancreatic cells failed to induce these changes (Figure 2). Moreover, these responses were sensitive to inhibition of cathepsin L, implicating this protease as the downstream molecular target of antibody-mediated neutralization of serpin molecules.
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