Chinese Journal of Tissue Engineering Research ›› 2023, Vol. 27 ›› Issue (在线): 1-.

   

Erastin inhibits proliferation of hypertrophic scar fibroblasts

He Xi1,3,4, Wan Yu1,3,4, Tang Yuting1,3,4, Yang Anning2,3, Wu Kai2, Jiao Yun5,Bai Zhigang6,Jiang Yideng2,3, Shen Jiangyong3   

  1. 1School of Clinical Medicine, 2School of Basic Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 3State Key Laboratory of Metabolic Cardiovascular Disease, National Health Commission of China, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 4Department of Burn Plastic Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 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 Revised:2022-09-06 Online:2023-01-08 Published:2022-09-24
  • Contact: Shen Jiangyong, Doctor's degree, 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, 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, No. U21A20343 (to JYD), No. 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, No. 2020BFH02003 (to YAN), No. 2020BFH02001 (to BZG), No. 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. Because there is no effective treatment, more effective treatment methods need to be sought.
Objective: To investigate the effect of ferroptosis inducer (Erastin) on the proliferation of human hypertrophic scar fibroblasts.
Methods: The hypertrophic scars provided by the Burn Plastic Surgery Department of the General Hospital of Ningxia Medical University and the normal skin of the same individual were collected, and human hypertrophic scar fibroblasts were extracted for subsequent experiments; 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 to measure cellular iron ion content; malondialdehyde (MDA) detection kit to detect cellular MDA content; 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 (treated with 20 μmol/L Erastin and 20 μmol/L Ferrostatin-1 for 24 hours) , qRT-PCR was used to detect the mRNA expression of proliferating cell nuclear antigen (PCNA) and cyclin-dependent kinase inhibitor (p27); Western blot was used to detect the protein expression of PCNA and p27; CCK8 and EdU were used to detect cell proliferation Vitality and proliferation levels.
Results And Conclusion: (1) Compared with the control group, the ferritin decreased (P < 0.01), the iron ions increased (P < 0.05), the MDA increased (P < 0.01). (2) Compared with the control group, the expression of PCNA decreased (mRNA: P < 0.01, protein: P < 0.01), the expression of p27 increased (mRNA: P < 
0.05, protein: P < 0.05), and the cell proliferation ability was weakened (P < 0.01), the number of EdU positive cells decreased (P < 0.01); (3) Compared with the ferroptosis inducer group, the expression of PCNA in the ferroptosis inducer + ferroptosis inhibitor group increased (mRNA: P<0.01, protein: P < 0.05), decreased p27 expression (mRNA: P < 0.01, protein: P < 0.05), enhanced cell proliferation (P < 0.01), and increased EdU-positive cells (P < 0.05). To conclude, the ferroptosis inducer (Erastin) induces ferroptosis in hypertrophic scar fibroblasts and then inhibits their proliferation, which provides a theoretical basis for finding a more effective clinical treatment method for hypertrophic scar.

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

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