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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 5

Hyaluronidase inhibits inflammation of the skin and colon.

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Hyaluronidase inhibits inflammation of the skin and colon.
(A and B) mRN...
(A and B) mRNA abundance of skin 3 days after infection with S. aureus measured by qPCR of IL-6 and Camp (n = 6 mice/group). WT mice are compared with Ella/hyal1 mice or mice after IV administration of PEGPH20. (C) Representative H&E histology at day 7 after DSS in distal colon sections of WT, Ella/hyal1, and PEGPH20-injected mice. (D) Daily body weight measurements normalized to original body weight in mice during administration of DSS (n = 5 mice/group). Statistics are performed by 1-way ANOVA multiple comparison test. Data in A and B are represented using box-and-whisker plots, with boxes representing the IQR, lines representing the median value, and whiskers representing minimum and maximum values, whereas data in D is represented as mean ± SEM; **P < 0.01 and ***P < 0.001 (Student’s t test). (E and F) RNA sequencing was performed on tissue extracted from the submucosal regions of the colon of control mice, mice treated with PEGPH20, mice treated for 7 days with DSS, or mice treated with DSS and PEGPH20. (E) Gene ontology analysis of transcripts induced by DSS that were inhibited by greater than 2-fold with PEGPH20. (F) Hierarchical clustering heat map of innate immune response–related genes.

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