Topical N-Acetylcysteine Accelerates Wound Healing in Vitro and in Vivo via the PKC/Stat3 Pathway

International Journal of Molecular Sciences

Min-Ling Tsai²  Hui-Pei Huang³  Jeng-Dong Hsu⁴  Yung-Rung Lai¹  Yu-Ping Hsiao²  Fung-Jou Lu² 

[1] Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 40201, Taiwan; E-Mail:;Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; E-Mails:;Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan; E-Mail:;Department of Pathology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan; E-Mail:

关键词: N-acetylcysteine;    wound healing;    glutathione;    MMP-1;    PKC;    Stat3;   

DOI  :  10.3390/ijms15057563

来源: mdpi

【 摘 要 】

N-Acetylcysteine (Nac) is an antioxidant administered in both oral and injectable forms. In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland