Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (5): 767-772.doi: 10.3969/j.issn.2095-4344.0541

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Phosphatase and tensin homolog regulates arthrofibrotic myofibroblast proliferation via PI3K/AKT signaling pathways

Zhuang Ze, Yu Dongjie, Yi Xiaoyou, Xiao Dahai, Jiang Shihai, He Ronghan, Wang Kun   

  1. Department of Joint Traumatology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
  • Revised:2018-04-02 Online:2019-02-18 Published:2019-02-18
  • Contact: Wang Kun, MD, Chief physician, Department of Joint Traumatology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
  • About author:Zhuang Ze, Master, Attending physician, Department of Joint Traumatology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
  • Supported by:

    the Medical Scientific Research Foundation of Guangdong Province, No. A2016066; a grant from the Scientific Research Project of Traditional Chinese Medicine of Guangdong Province, No. 20181061

Abstract:

BACKGROUND: There are few reports about the genes that regulate the expression of myofibroblasts in rats with arthrofibrosis. The expression of tumor suppressor gene phosphatase and tensin homolog (PTEN) in fibrosis tissues has not yet been reported.
OBJECTIVE: To investigate the expression of PTEN gene in articular capsule tissue in rats with arthrofibrosis and the significance of PI3K/AKT signaling pathway in arthrofibrosis. 
METHODS: The rat model of arthrofibrosis was established by knee fixation, and the posterior articular capsule of knee joint was removed. Myofibroblasts were isolated and cultured by tissue explant method. The expression level of PTEN mRNA was detected by quantitative real-time PCR. The protein expression levels of COL1-A1, and PTEN in myofibroblasts and the signal molecules change in downstream PI3K/AKT signaling pathway were detected by western blot assay. The PI3K/AKT signal pathway specific blocker LY294002 was used to observe the changes of myofibroblast proliferation.
RESULTS AND CONCLUSION: The expression levels of PTEN mRNA and protein in arthrofibrosis were significantly down-regulated compared with the normal articular group (P < 0.05). The down-regulated expression level of PTEN could up-regulate the expression levels of PI3K and AKT signaling molecules (P < 0.05) and enhanced the proliferation of myofibroblasts. After application of the PI3K/AKT blocker LY294002, the proliferation of myofibroblasts was inhibited. Our results suggest that there is a down-regulation in PTEN expression in articular capsule tissue of rats with arthrofibrosis, and PTEN regulates the development of articular capsule tissue fibrosis via PI3K/AKT signaling pathway. 


中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

Key words: Fibrosis, Fibroblasts, Tissue Engineering

CLC Number: