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Reduced Expression of YAP in Dermal Fibroblasts is Associated with Impaired Wound Healing in Type 2 Diabetic Mice

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Dermal fibroblasts play essential roles in wound healing and their dysfunction has been shown to be associated with impaired wound healing in diabetes. In the present study, we aimed at investigating whether Yes-associated protein (YAP), a mediator of mechanotransduction in dermal fibroblasts, is associated with impaired wound healing in diabetic mice. Compared with that in the control, the rate of wound contraction was decreased twofold in db/db type 2 diabetic mice (db/db mice). To mimic diabetic pathological condition, dermal fibroblasts were cultured under high glucose conditions (25.5 mM glucose). Further, dermal fibroblast-mediated contraction of wound was evaluated by in vitro collagen gel contraction assay. Dermal fibroblasts cultured under hyperglycemic condition showed impaired gel contraction and mitochondrial dysfunction, compared to the cells cultured under normoglycemic conditions (5.5 mM glucose). Importantly, compared with the normal dermal fibroblasts, diabetic db/db dermal fibroblasts expressed lower levels of growth factors and cytokines that enhance wound healing, such as insulin-like growth factor-1, stromal cell-derived factor-1, connective tissue growth factor, and transforming growth factor-β (TGF-β). The quantity of YAP mRNA was also lower in diabetic db/db dermal fibroblasts, compared with that in the control fibroblasts. These results indicate that impaired wound healing in diabetics is associated with the dysfunction of dermal fibroblasts, including downregulation of YAP, which plays essential roles in extracellular matrix remodeling and TGF-β-mediated wound healing.

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Acknowledgements

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2015R1D1A1A09057839), the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI13C1479), and a grant from Kyung Hee University in 2016 (KHU-20160701).

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Authors and Affiliations

  1. Department of Genetic Engineering, Graduate School of Biotechnology, Kyung Hee University, Yong-In, 17104, Korea

    Jinyeong Yu, Sanghyuk Choi & Jihyun Um

  2. East-West Medical Research Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Korea

    Ki-Sook Park

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  1. Jinyeong Yu
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  2. Sanghyuk Choi
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Correspondence to Ki-Sook Park.

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All of the authors of this manuscript declare that they have no conflict of interest.

Ethical statement

All animal experiments were performed in compliance with protocols approved by the Institutional Animal Care and Use of Kyung Hee University (KHMC-IACUC 15-020).

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Yu, J., Choi, S., Um, J. et al. Reduced Expression of YAP in Dermal Fibroblasts is Associated with Impaired Wound Healing in Type 2 Diabetic Mice. Tissue Eng Regen Med 14, 49–55 (2017). https://doi.org/10.1007/s13770-016-0019-9

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  • DOI: https://doi.org/10.1007/s13770-016-0019-9

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