Ghrelin Inhibits ACL Derived Fibroblasts Pyroptosis and Promotes Migration Through Regulating NF-κB p65/NLRP3 Signaling

作者：Zhu, Xu; Wu, Juan; Zheng, Shao-Wei; Liu, Gang; Zou, Yu-Cong^*

来源：International Journal of Peptide Research and Therapeutics, 2023, 29(2): 19.

DOI：10.1007/s10989-023-10490-w

• Ghrelin
• Pyroptosis
• Anterior cruciate ligament injury
• Fibroblasts
• NF-kappa B
• NLRP3

To explore whether Ghrelin could inhibit anterior cruciate ligament (ACL) derived fibroblasts pyroptosis and promote migration through regulating NF-kappa B p65/NLRP3 signaling. In this study, fibroblasts extracted from the ACL of clinical patients were collected for subsequent cellular experiments and to determine the model of TNF-alpha cell inflammation and the optimal concentration of Ghrelin intervention. An ACL partial injury model was established in Sprague Dawley rats given Ghrelin or Saline intervention. The repair of the ACL injury was determined by detecting the expression of pyroptosis molecules in ACL fibroblasts, changes in migration capacity, and histological staining. Cell migration was significantly inhibited in the TNF-alpha inflammation model group compared to the control group, and the expression of cellular pyroptosis proteins was significantly increased. Ghrelin intervention improved cell migration and inhibited the expression of pyroptosis proteins. Further study revealed that the expression of NF-kappa B p65/NLRP3 was also significantly reduced, suggesting that Ghrelin may inhibit the pyroptosis of fibroblasts by suppressing NF-kappa B p65/NLRP3. In Sprague Dawley rats with partial ACL injury, Ghrelin treatment for 4 or 8 weeks promoted ACL repair by increasing the number of fibroblasts and optimizing the distribution of collagen fibers compared to the injury group. Our study illustrates the ability of Ghrelin to inhibit pyroptosis and improve cell migration ability, thereby promoting repair of injured ACLs, which will provide a new strategy for the treatment of ACL injuries.

• 单位
  南方医科大学; 5