Basic—Alimentary TractReg IV Regulates Normal Intestinal and Colorectal Cancer Cell Susceptibility to Radiation-Induced Apoptosis
Section snippets
Cell Lines and Culture
The human CRC cell lines HCT116, SW480, and HT29 (American Type Culture Collection, Manassas, VA) were grown in Dulbecco's modified Eagle medium (Cambrex, Walkersville, MD) containing 10% heat-inactivated fetal bovine serum (HyClone, Logan, UT).
Anti–Reg IV Specific Polyclonal Antibody and mAbs
Armenian hamster mAbs (2H6 and 3E5) and rabbit polyclonal antibody (α-Reg IV 4261) against human Reg IV protein as well as recombinant human Reg IV protein (rhR4) were produced and characterized with the help of the Hybridoma Center at the Washington
Reg IV Inhibits IR-Induced Intestinal Cell Apoptosis
We previously showed that Reg IV regulates apoptosis in human CRC cells.6, 12 However, its role in normal GI cells was not established. In the present study, we used a murine model of IR-induced intestinal injury to determine the role of Reg IV in normal GI cell apoptosis. Following immunodetection of Reg IV–positive cells in distal jejunum sections using an α-Reg IV 4261 antibody, IR exposures led to a dose-dependent decrease in Reg IV expression (Figure 1A). Furthermore, IR (6 Gy) exposure to
Discussion
The normal GI epithelial architecture is frequently disrupted following injury. The homeostasis in a normal GI epithelial cell population is maintained by their continuous replacement with replicating undifferentiated epithelial cells (transit cells) located in the crypts, followed by their subsequent differentiation and migration away from the zone of replication.24, 25 Crypt stem cells play a central role in maintaining GI architecture both in normal and injury states.23, 26 Stem cells
Acknowledgments
Repository URL and data accession numbers: hybridoma cell lines 2H6.3.1 and 3E5.4.1 (http://pathology.wustl.edu/research/hybridoma.php; fusion no. 4465), Reg IV mRNA (GenBank accession no. NM_032044).
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2019, Clinical Colorectal CancerCitation Excerpt :The regenerating islet-derived gene 4 (REG4) is one of a family of genes (Reg) belonging to the calcium-dependent lectin superfamily, encoding a group of small secretory proteins. These have been found to be constitutively expressed in cell lines of the gastrointestinal tract with characteristic up-regulation in RC at both messenger RNA (mRNA) and peptide levels.75,76 In cellular models, it has been shown to activate cell proliferation, in addition to in vitro migration and invasion of CRC cells.77
Recombinant Reg3α protein protects against experimental acute pancreatitis in mice
2016, Molecular and Cellular EndocrinologyCitation Excerpt :Our results displayed that the contents of Bcl-2 and Bcl-xL were significantly increased in the pancreas of AP mice when treated with rReg3α [Fig. 5A and B], indicating that the protective effect of rReg3α could be led by the increased levels of Bcl-2 and Bcl-xL. Another study also explored that both recombinant and endogenous overexpressed Reg4 enhanced the resistance against radiotherapy in normal intestinal and colorectal cancer cells, which was mediated by the upregulated expressions of Bcl-2 and Bcl-xL (Bishnupuri et al., 2010). PARP is a class of proteins responsible for DNA repair while its overactivation causes the depletion of cellular NAD+ and induces cell necrosis (Isabelle et al., 2010).
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by National Institutes of Health grants DK060106 and P30 DK52574 (to B.K.D.) and grants DK62265 and CA109269 (to S.A.).