Tissue Eng Regen Med.  2017 Feb;14(1):49-55. 10.1007/s13770-016-0019-9.

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

• Yu J
• Choi S
• Um J
• Park KS

• KMID: 2371103
• DOI: http://doi.org/10.1007/s13770-016-0019-9

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.

Keyword

Dermal fibroblast; Diabetes; Wound; YAP

MeSH Terms

Animals
Collagen
Connective Tissue Growth Factor
Cytokines
Down-Regulation
Extracellular Matrix
Fibroblasts*
Glucose
In Vitro Techniques
Intercellular Signaling Peptides and Proteins
Mice*
RNA, Messenger
Wound Healing*
Wounds and Injuries*
Collagen
Connective Tissue Growth Factor
Cytokines
Glucose
Intercellular Signaling Peptides and Proteins
RNA, Messenger