Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

VDUP1 Deficiency Promotes the Severity of DSS-Induced Colitis in Mice by Inducing Macrophage Infiltration

Version 1 : Received: 25 July 2023 / Approved: 25 July 2023 / Online: 26 July 2023 (05:28:59 CEST)

A peer-reviewed article of this Preprint also exists.

Park, K.H.; Lee, H.; Kim, H.-C.; Choi, I.; Han, S.-B.; Kang, J.S. VDUP1 Deficiency Promotes the Severity of DSS-Induced Colitis in Mice by Inducing Macrophage Infiltration. Int. J. Mol. Sci. 2023, 24, 13584. Park, K.H.; Lee, H.; Kim, H.-C.; Choi, I.; Han, S.-B.; Kang, J.S. VDUP1 Deficiency Promotes the Severity of DSS-Induced Colitis in Mice by Inducing Macrophage Infiltration. Int. J. Mol. Sci. 2023, 24, 13584.

Abstract

The loss of vitamin D3 upregulated protein 1 (VDUP1) has been implicated in the pathogenesis of various inflammation-related diseases. Notably, reduced expression of VDUP1 has been observed in clinical specimens of ulcerative colitis (UC). However, the role of VDUP1 deficiency in colitis remains unclear. In this study, we investigated the role of VDUP1 in dextran sulfate sodium (DSS)-induced experimental colitis in mice. VDUP1-deficient mice were more susceptible to DSS-induced colitis than their wild-type (WT) littermates after 2% DSS administration. VDUP1-deficient mice exhibited an increased disease activity index (DAI) and histological scores, as well as significant colonic goblet cell loss and an increase in apoptotic cells. These changes were accompanied by a significant decrease in MUC2 mRNA expression and a marked increase in proinflammatory cytokines and chemokines within damaged tissues. Furthermore, phosphorylated NF-B p65 expression was significantly upregulated in damaged tissues in the context of VDUP1 deficiency. VDUP1 deficiency also led to significant infiltration of macrophages into the site of ulceration. An in vitro chemotaxis assay confirmed that VDUP1 deficiency enhanced bone marrow-derived macrophage (BMDM) chemotaxis induced by CCL2. Overall, the loss of VDUP1 plays a critical role in the pathogenesis of UC, and blocking VDUP1 dissociation may represent a promising therapeutic strategy for the treatment of UC.

Keywords

VDUP1; inflammation; macrophage infiltration; NF-B; ulcerative colitis

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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