Possible role of ginsenoside Rb1 in skin wound healing via regulating senescent skin dermal fibroblast

Journal Article · Tue May 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.03.170· OSTI ID:23137183

Hou, Jingang ^[1]; Kim, Sunchang ^[1]

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1. Intelligent Synthetic Biology Center, Daejeon 34141 (Korea, Republic of)

Highlights: • Senescent human skin fibroblast secrets PDGF, TGF and VEGF to promote skin wound healing process. • Ginsenoside Rb1 enhances senescent fibroblast to secret growth factors and myofibroblast differentiation. • Ginsenoside Rb1 regulates senescent fibroblast through p38MAPK/MSK2/NF-κB pathway. Cellular senescence suppresses cancer by inducing irreversible cell growth arrest. Nevertheless, senescent cells is proposed as causal link with aging and aging-related pathologies. The physiological beneficial functions of senescent cells are still of paucity. Here we show that senescent human dermal fibroblast accelerates keratinocytes scratch wound healing and stimulates differentiation of fibroblast. Using oxidative stress (100 μM H{sub 2}O{sub 2} exposure for 1 h) induction, we successfully triggered fibroblast senescence and developed senescence associated secretory phenotype (SASP). The induction of SASP was regulated by p38MAPK/MSK2/NF-κB pathway. Interestingly, inhibition of p38MAPK activation only partially suppressed SASP. However, SASP was significantly inhibited by SB747651A, a specific MSK inhibitor. Additionally, we demonstrate that SASP stimulates migration of keratinocytes and myofibroblast transition of fibroblast, through fold-increased secretion of growth factors, platelet-derived growth factor AA (PDGF-AA) and AB (PDGF-AB), transforming growth factor beta 1 (TGF-β1) and beta 2 (TGF-β2), vascular endothelial growth factor A (VEGF-A) and D (VEGF-D), vascular endothelial growth factor receptor 2 (VEGFR2) and 3 (VEGFR3). Importantly, we also confirmed ginsenoside Rb1 promoted SASP-mediated healing process via p38MAPK/MSK2/NF-κB pathway. The results pointed to senescent fibroblast as a potential mechanism of wound healing control in human skin. Further, it provided a candidate targeted for wound therapy.

• OSTI ID: 23137183
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 499; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
FIBROBLASTS
GROWTH FACTORS
HYDROGEN PEROXIDE
NEOPLASMS
RECEPTORS
SKIN
WOUNDS