Chinese Journal of Tissue Engineering Research ›› 2023, Vol. 27 ›› Issue (32): 5120-5125.doi: 10.12307/2023.539

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Erastin inhibits proliferation of hypertrophic scar fibroblasts

He Xi1, 2, 3, Wan Yu1, 2, 3, Tang Yuting1, 2, 3, Yang Anning2, 4, Wu Kai4, Jiao Yun5, Bai Zhigang6, Jiang Yideng2,4, Shen Jiangyong3   

  1. 1School of Clinical Medicine, 2State Key Laboratory of Metabolic Cardiovascular Disease, National Health Commission of China, 4School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 3Department of Burn Plastic Surgery, 5Department of Infection, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 6Department of Orthopedics, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Received:2022-08-02 Accepted:2022-09-06 Online:2023-11-18 Published:2023-03-23
  • Contact: Shen Jiangyong, MD, Associate professor, Department of Burn Plastic Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • About author:He Xi, Master candidate, School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; State Key Laboratory of Metabolic Cardiovascular Disease, National Health Commission of China, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Department of Burn Plastic Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Supported by:
    The National Natural Science Foundation of China, Nos. U21A20343 (to JYD) and 81860555 (to SJY); Basic Research Funds of the Central Public Welfare Research Institutes of the Chinese Academy of Medical Sciences, No. 2019PT330002 (to JYD); The Key Project of Ningxia Hui Autonomous Region's Key R&D Plan, Nos. 2020BFH02003 (to YAN), 2020BFH02001 (to BZG), and 2021BEG02028 (to WK); First-class Discipline Construction Project in Ningxia Colleges and Universities (Construction of Domestic First-Class Discipline Clinical Medicine in Ningxia Medical University), No. NXYLXK2017A05 (to SJY)

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Abstract: BACKGROUND: Hypertrophic scar is a kind of pathological scar that appears in the healing process after skin trauma caused by various reasons and there is no effective treatment.
OBJECTIVE: To investigate the effect of ferroptosis inducer (Erastin) on the proliferation of human hypertrophic scar fibroblasts.
METHODS: Hypertrophic scar samples provided by the Burn Plastic Surgery Department of the General Hospital of Ningxia Medical University and normal skin samples of the same individual were collected. Human hypertrophic scar fibroblasts were then extracted for subsequent experiments. (1) The cells were divided into control group (without treatment) and ferroptosis inducer group (treated with 20 μmol/L Erastin for 24 hours). The expression of Ferritin was detected by western blot. Iron ion detection kit was used to measure cellular iron ion concentration. Malondialdehyde detection kit was used to detect cellular malondialdehyde content. (2) The cells were divided into control group (without treatment), ferroptosis inducer group (treated with 20 μmol/L Erastin for 24 hours) and ferroptosis inducer+ferroptosis inhibitor group (co-treated with 20 μmol/L Erastin and 20 μmol/L Ferrostatin-1 for 24 hours). The mRNA and protein expressions of proliferating cell nuclear antigen (PCNA) and cyclin-dependent kinase inhibitor (p27) were detected using qRT-PCR and western blot. Cell counting kit-8 and EdU were used to detect cell proliferation viability and levels.
RESULTS AND CONCLUSION: Compared with the control group, Erastin decreased the ferritin expression (P < 0.01), increased the content of iron ions (P < 0.05), and elevated the malondialdehyde content in the cells (P < 0.01). Compared with the control group, Erastin decreased the expression of PCNA (P < 0.01), increased the expression of p27 (P < 0.05), weakened the cell proliferation ability (P < 0.01), and reduced the number of EdU-positive cells (P < 0.01). Compared with the ferroptosis inducer group, the ferroptosis inducer + ferroptosis inhibitor group had increased expression of PCNA (P < 0.05), decreased p27 expression (P < 0.05), enhanced cell proliferation (P < 0.01), and increased number of EdU-positive cells (P < 0.05). To conclude, the ferroptosis inducer (Erastin) induces ferroptosis in hypertrophic scar fibroblasts and then inhibits their proliferation.

Key words: ferroptosis inducer, Erastin, PCNA, p27, hypertrophic scar, fibroblast, ferroptosis, proliferation

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