Palmitoylethanolamide (PEA) reduces postoperative adhesions after experimental strabismus surgery in rabbits by suppressing canonical and non-canonical TGFβ signaling through PPARα

• Published in: Biochemical pharmacology 2021-02, Vol.184, p.114398-114398, Article 114398
• Main Authors: Li, Yitian, Zhao, Sichen, Xu, Sennan, Li, Yuhang, Wang, Chaowei, Ren, Jie, Li, Fei, Hu, Xiaokun, Lin, Kuantian, Qiu, Yan, Xiu, Yanghui
• Format: Article
• Language: English
• Subjects: Adhesions; Amides - pharmacology; Amidohydrolases - antagonists & inhibitors; Amidohydrolases - metabolism; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Ethanolamines - pharmacology; Fibrosis; HEK293 Cells; Humans; Male; MAP Kinase Kinase Kinases - antagonists & inhibitors; Mice; NIH 3T3 Cells; Oxazolidinones - pharmacology; Palmitic Acids - pharmacology; Palmitoylethanolamide (PEA); peroxisome proliferator-activated receptor α (PPARα); Postoperative Complications - drug therapy; Postoperative Complications - etiology; PPAR alpha - metabolism; Rabbits; Strabismus; Strabismus - surgery; TGFβ-activated kinase 1 (TAK1); Tissue Adhesions - drug therapy
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2020.114398

[Display omitted] Postoperative adhesions and scarring are the particular complication after strabismus surgery, for which there is currently no comprehensive treatment available. Preventing inflammation and fibrosis in the extraocular muscle are crucial for treatment of postoperative adhesions. In the present study, we found that administration of palmitoylethanolamide (PEA) attenuated postoperative inflammation and fibroproliferation through activating peroxisome proliferator-activated receptor α (PPARα), thus prevented scar formation. Inhibition of PEA degradation by N-Acylethanolamine acid amidase (NAAA) inhibitor F96 led to the same pharmacological results. PPARα activation suppressed both canonical and non-canonical TGFβ signaling. Mechanistically, we found that PPARα directly bound to TGFβ-activated kinase 1 (TAK1), thus preventing its hyperphosphorylation and the activation of downstream p38 and JNK1/2 signaling. Taken together, current study suggested that PEA could be a novel therapeutic approach for postoperative adhesions after strabismus surgery.