Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/89474
Title: Angiopoietin-like 4 induces a β-catenin-mediated upregulation of ID3 in fibroblasts to reduce scar collagen expression
Authors: Teo, Ziqiang
Chan, Jeremy Soon Kiat
Chong, Han Chung
Sng, Ming Keat
Choo, Chee Chong
Phua, Glendon Zhi Ming
Teo, Daniel Jin Rong
Zhu, Pengcheng
Choong, Cleo Swee Neo
Wong, Marcus Thien Chong
Tan, Nguan Soon
Keywords: Collagen Expression
Fibroblasts
Issue Date: 2017
Source: Teo, Z., Chan, J. S. K., Chong, H. C., Sng, M. K., Choo, C. C., Phua, G. Z. M., et al. (2017). Angiopoietin-like 4 induces a β-catenin-mediated upregulation of ID3 in fibroblasts to reduce scar collagen expression. Scientific Reports, 7(1), 6303-.
Series/Report no.: Scientific Reports
Abstract: In adult skin wounds, collagen expression rapidly re-establishes the skin barrier, although the resultant scar is aesthetically and functionally inferior to unwounded tissue. Although TGFβ signaling and fibroblasts are known to be responsible for scar-associated collagen production, there are currently no prophylactic treatments for scar management. Fibroblasts in crosstalk with wound keratinocytes orchestrate collagen expression, although the precise paracrine pathways involved remain poorly understood. Herein, we showed that the matricellular protein, angiopoietin-like 4 (ANGPTL4), accelerated wound closure and reduced collagen expression in diabetic and ANGPTL4-knockout mice. Similar observations were made in wild-type rat wounds. Using human fibroblasts as a preclinical model for mechanistic studies, we systematically elucidated that ANGPTL4 binds to cadherin-11, releasing membrane-bound β-catenin which translocate to the nucleus and transcriptionally upregulate the expression of Inhibitor of DNA-binding/differentiation protein 3 (ID3). ID3 interacts with scleraxis, a basic helix-loop-helix transcription factor, to inhibit scar-associated collagen types 1α2 and 3α1 production by fibroblasts. We also showed ANGPTL4 interaction with cadherin-11 in human scar tissue. Our findings highlight a central role for matricellular proteins such as ANGPTL4 in the attenuation of collagen expression and may have a broader implication for other fibrotic pathologies.
URI: https://hdl.handle.net/10356/89474
http://hdl.handle.net/10220/44977
ISSN: 2045-2322
DOI: 10.1038/s41598-017-05869-x
Rights: © 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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