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SerpinB13 antibodies promote β cell development and resistance to type 1 diabetes

Sci Transl Med. 2021-04; 
Yury Kryvalap, Matthew L Jiang, Nadzeya Kryvalap, Cole Hendrickson, Jan Czyzyk
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Insect Expression … Purified recombinant serpinB13 expressed in baculovirus was obtained from GenScript and used as a … Invitrogen) and expressed for 48 hours in 293 cells using Lipofectamine 2000 … Get A Quote

摘要

Pancreatic endocrine cell development is dependent on the rescue of the neurogenin3 (Ngn3) transcription factor from repression by Notch. The signals that prevent Notch signaling, thereby allowing the formation of pancreatic endocrine cells, remain unclear. We show that inhibiting serpinB13, a cathepsin L (CatL) protease inhibitor expressed in the pancreatic epithelium, caused in vitro and in vivo cleavage of the extracellular domain of Notch1. This was followed by a twofold increase in the Ngn3 progenitor cell population and enhanced conversion of these cells to express insulin. Conversely, both recombinant serpinB13 protein and CatL deficiency down-regulated pancreatic Ngn3 cell output. Mouse embryonic exposu... More

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