Resveratrol inhibits proliferation and promotes apoptosis of keloid fibroblasts by targeting HIF-1α

被引:34
作者
Si, Loubin [1 ]
Zhang, Mingzi [1 ]
Guan, Enling [2 ]
Han, Qin [2 ]
Liu, Yifang [5 ]
Long, Xiao [1 ]
Long, Fei [1 ]
Zhao, Robert Chun-Hua [3 ,4 ]
Huang, Jiuzuo [1 ]
Liu, Zhifei [1 ]
Zhao, Ru [1 ]
Zhang, Hailin [1 ]
Wang, Xiaojun [1 ]
机构
[1] Peking Union Med Coll Hosp, Dept Plast Surg, Shuaifuyuan 1, Beijing 100730, Peoples R China
[2] Qingdao Huangdao Dist Hosp Tradit Chinese Med, Dept Ear Nose Throat, Qingdao, Shandong, Peoples R China
[3] Chinese Acad Med Sci & Peking Union Med Coll, Ctr Excellence Tissue Engn, Inst Basic Med Sci, Beijing, Peoples R China
[4] Chinese Acad Med Sci & Peking Union Med Coll, Sch Basic Med, Beijing, Peoples R China
[5] Beijing Vocat Coll Agr, Int Educ Coll, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
keloid; resveratrol; HIF-1; alpha; collagen synthesis; hypoxia; HYPOXIA; COLLAGEN; EXPRESSION; CELLS; METABOLISM; MIGRATION; FIBROSIS; INVASION;
D O I
10.1080/2000656X.2020.1771719
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
100224 [整形外科学];
摘要
A keloid is characterized by red, tickling, hard, and irregular raised tissues, and it tends to outgrow its origin. It frequently occurs in young adults and appears to be refractory to prevailing therapies. Resveratrol is a new drug that has anti-proliferative effect. In this study, keloid-derived fibroblasts were cultured under hypoxia environment and was treated by resveratrol. CCK-8 assay and Annexin V-FITC were used to evaluate cell activity and apoptosis level. Western blot and RT-qPCR were also used to assess the expression of HIF-alpha, Collagen I and Collagen III. Besides, siRNA was also used to explore the mechanisms of resveratrol's effect. In this study, hypoxia promotes proliferation and inhibits apoptosis of keloid fibroblasts. These findings highlight the potential obstacle in treating keloids. Furthermore, we demonstrated that resveratrol could reverse the effect of hypoxia on keloids through down-regulation of HIF-1 alpha. Moreover, collagen synthesis in keloid fibroblasts was also inhibited by resveratrol, which corresponded with HIF-1 alpha suppression. These results provide evidence for resveratrol's treatment effect against keloids through inhibiting cell proliferation and promoting cell apoptosis, while, HIF-1 alpha may play the key role in this process.
引用
收藏
页码:290 / 296
页数:7
相关论文
共 40 条
[21]
Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro [J].
Ma, Xiaoyang ;
Chen, Jia ;
Xu, Bei ;
Long, Xiao ;
Qin, Han ;
Zhao, Robert Chunhua ;
Wang, Xiaojun .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2015, 35 (05) :1246-1256
[22]
Hypoxia-Inducible Factors and the Response to Hypoxic Stress [J].
Majmundar, Amar J. ;
Wong, Waihay J. ;
Simon, M. Celeste .
MOLECULAR CELL, 2010, 40 (02) :294-309
[23]
Co-targeting the IGF system and HIF-1 inhibits migration and invasion by (triple-negative) breast cancer cells [J].
Mancini, M. ;
Gariboldi, M. B. ;
Taiana, E. ;
Bonzi, M. C. ;
Craparotta, I. ;
Pagin, M. ;
Monti, E. .
BRITISH JOURNAL OF CANCER, 2014, 110 (12) :2865-2873
[24]
Effects of resveratrol on HepG2 cells as revealed by 1H-NMR based metabolic profiling [J].
Massimi, Mara ;
Tomassini, Alberta ;
Sciubba, Fabio ;
Sobolev, Anatoli P. ;
Devirgiliis, Laura Conti ;
Miccheli, Alfredo .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2012, 1820 (01) :1-8
[25]
The evidence for natural therapeutics as potential anti-scarring agents in burn-related scarring [J].
Mehta, M. ;
Branford, O. A. ;
Rolfe, K. J. .
BURNS & TRAUMA, 2016, 4
[26]
Intralesional 5-fluorouracil as a treatment modality of keloids [J].
Nanda, S ;
Reddy, BSN .
DERMATOLOGIC SURGERY, 2004, 30 (01) :54-57
[27]
Abnormalities in collagen composition may contribute to the pathogenesis of hemorrhoids: morphometric analysis [J].
Nasseri, Y. Y. ;
Krott, E. ;
Van Groningen, K. M. ;
Berho, M. ;
Osborne, M. C. ;
Wollman, S. ;
Weiss, E. G. ;
Wexner, S. D. .
TECHNIQUES IN COLOPROCTOLOGY, 2015, 19 (02) :83-87
[28]
Hypoxia induces chemoresistance in ovarian cancer cells by activation of signal transducer and activator of transcription 3 [J].
Selvendiran, Karuppaiyah ;
Bratasz, Anna ;
Kuppusamy, M. Lakshmi ;
Tazi, Mia F. ;
Rivera, Brian K. ;
Kuppusamy, Periannan .
INTERNATIONAL JOURNAL OF CANCER, 2009, 125 (09) :2198-2204
[29]
Liposome-Adenoviral hTERT-siRNA Knockdown in Fibroblasts from Keloids Reduce Telomere Length and Fibroblast Growth [J].
Shang, Yong ;
Yu, Dongmei ;
Hao, Lijun .
CELL BIOCHEMISTRY AND BIOPHYSICS, 2015, 72 (02) :405-410
[30]
Extracellular matrix molecules implicated in hypertrophic and keloid scarring [J].
Sidgwick, G. P. ;
Bayat, A. .
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, 2012, 26 (02) :141-152