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Hyaluronidase inhibits reactive adipogenesis and inflammation of colon and skin
Tatsuya Dokoshi, … , Mikihiro Fujiya, Richard L. Gallo
Tatsuya Dokoshi, … , Mikihiro Fujiya, Richard L. Gallo
Published November 2, 2018
Citation Information: JCI Insight. 2018;3(21):e123072. https://doi.org/10.1172/jci.insight.123072.
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Research Article Dermatology Inflammation

Hyaluronidase inhibits reactive adipogenesis and inflammation of colon and skin

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Abstract

In this study we evaluated the role of hyaluronan (HA) in reactive adipogenesis, a local expansion of preadipocytes that provides host defense by release of antimicrobial peptides. We observed that HA accumulated during maturation of adipocytes in vitro and was associated with increased expression of preadipocyte factor 1, zinc finger protein 423, and early B cell factor 1. Although HA is normally abundant in the extracellular matrix, a further increase in HA staining occurred in mice at sites of reactive adipogenesis following injury of colon by dextran sodium sulfate or injury of skin from infection with Staphylococcus aureus. HA also abundantly accumulated around adipocytes seen in the colons of patients with inflammatory bowel disease. This HA was necessary for adipocyte maturation because digestion of HA by administration of soluble hyaluronidase or transgenic expression of hyaluronidase 1 inhibited adipogenesis in vitro and in vivo. Furthermore, hyaluronidase also suppressed inflammation of both skin and colon and decreased antimicrobial peptide expression by developing preadipocytes. This resulted in increased bacterial transit across the epithelial barrier despite decreased tissue injury from inflammation. These observations suggest HA plays an important role in reactive adipogenesis and host defense after injury.

Authors

Tatsuya Dokoshi, Ling-juan Zhang, Teruaki Nakatsuji, Christopher A. Adase, James A. Sanford, Rudolph D. Paladini, Hiroki Tanaka, Mikihiro Fujiya, Richard L. Gallo

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Figure 2

An increase in adipose occurs during experimental colitis.

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An increase in adipose occurs during experimental colitis.
(A) Represent...
(A) Representative anatomical and (B) histological images of the distal colon from mice at day 0 and day 7 or 42 days after being provided with 3% DSS in drinking water. Tissue was stained with hematoxylin and eosin. Brackets delineate submucosal region occupied by adipocytes. Scale bar: 50 microns. (C) Transcripts identified by RNA sequencing to be increased or decreased after 7 days of DSS (2-fold change vs. normal colon). (D) Gene ontology analysis of the upregulated genes by DSS treatment. (E) Reverse transcription qPCR (RTqPCR) of the relative abundance of transcripts for Pref1, Zfp423, and Ebf1, as normalized to β-actin (n = 5 mice/group). Data in E is represented using box-and-whisker plots, with boxes representing the IQR, lines representing the median value, and whiskers representing minimum and maximum values; *P < 0.05, **P < 0.01, and ***P < 0.001 (Student’s t test). (F and G) β-Gal staining of the Zfp423LacZ/+ mice colon 7 days after DSS. (H) Representative histology of uninvolved Crohn’s disease human patient tissues stained with anti-PREF1/DLK antibody. Scale bar: 10 microns. (I) Representative histology of involved Crohn’s disease human patient tissues stained with anti-PREF1/DLK antibody. Scale bar: 10 microns.

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