Lumican alleviates hypertrophic scarring by suppressing integrin-FAK signaling.
Hypertrophic scarring (HS) is an overcompensation of wound healing that increases the risk of cosmetic disfigurement and functional impairment. No gold standard has been established for the treatment or prevention of HS. Our study aims to elucidate the expression and function of lumican in the pathogenesis of HS as well as the underlying mechanism involved in this procedure. An animal model of HS (rabbit ear) was established, and the Ad-lumican vectors were locally injected. Primary fibroblasts isolated from patients with hypertrophic burn scars were used in vitro. Histological and molecular changes in HS pathogenesis were evaluated. The results showed that lumican is significantly reduced in HS tissues and fibroblasts from HS patients as compared to normal skin or cells. Lumican levels were further suppressed in response to TGF-β stimulation. However, lumican upregulation effectively thinned the scar area and inhibited fibroblast proliferation and the cell cycle. Meanwhile, Ad-lumican administration suppressed the deposition of extracellular matrix, such as collagen and CTGF. Ad-lumican injected animals or fibroblasts presented comparable integrin α2β1expression while greatly reduced phosphorylation of FAK compared to the negative control. Moreover, Ad-lumican administration largely enhanced the binding of lumican to integrin α2β1and may thus inhibit the signaling propagation of collagen-integrin α2β1. Overall, the restoration of lumican levels contributed to suppressing the HS progression by inhibiting collagen-integrin α2β1-FAK signaling.
Department of Plastic Surgery, Tangdu Hospital, Fourth Military Medical University, Shaan xi, Xi'an 710038, China.
Yuqian
Y
Zhao
Department of Plastic Surgery, Tangdu Hospital, Fourth Military Medical University, Shaan xi, Xi'an 710038, China. Electronic address: yuyong@fmmu.edu.cn.
Xueyong
X
Li
Department of Plastic Surgery, Tangdu Hospital, Fourth Military Medical University, Shaan xi, Xi'an 710038, China.
Xiaoli
X
Xu
Department of Plastic Surgery, Tangdu Hospital, Fourth Military Medical University, Shaan xi, Xi'an 710038, China.
Zhi
Z
He
Department of Plastic Surgery, Tangdu Hospital, Fourth Military Medical University, Shaan xi, Xi'an 710038, China.
Lei
L
Cui
Department of Plastic Surgery, Tangdu Hospital, Fourth Military Medical University, Shaan xi, Xi'an 710038, China.
Xiaoxing
X
Lv
D000818:Animals; D049109:Cell Proliferation; D017439:Cicatrix, Hypertrophic / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D000071234:Lumican / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011817:Rabbits; D015398:Signal Transduction; D014945:Wound Healing / Q000502:physiology
D016023:Integrins; C000604306:LUM protein, human; D000071234:Lumican; D003094:Collagen; D051416:Focal Adhesion Protein-Tyrosine Kinases
Lumican