The activation of FPR3/PKA/Rap1/ERK1/2 and FPR3/p-IκB/NF-κB axis in fibroblasts promote capsular contracture after rhinoplasty.

Background: Capsular contracture may occur after rhinoplasty due to rejection of silicone implants by the immune system. Our previous high-throughput sequencing of RNA in nasal capsular contracture tissue revealed that FPR3 was significantly increased in grade IV capsular contracture tissue, compared with grade II.

Objective: This study aimed to elucidate the effect and specific mechanism of FPR3 on capsular formation and contracture following rhinoplasty.

Methods: Using the GeneMANIA Database, the genes involved with FPR3 expression were searched, and the Gene Ontology analysis was performed to annotate the biological functions of the aforementioned genes. The mRNA and protein expressions of related genes in fibroblasts and capsular contracture tissues were analyzed using quantitative real-time PCR, western blot, and immunohistochemical staining. CCK-8 was used to determine the viability of cells. The migration capacity of fibroblasts was assessed using a wound healing assay. ELISA was used to detect levels of IL-1β, TNF-α, and IL-6.

Results: After rhinoplasty, the expression of FPR3 in the capsular tissue increased in proportion to the degree of contracture. By activating the PKA/Rap1/ERK1/2 axis, overexpression of FPR3 can significantly increase the cell viability of fibroblasts and promote their transformation into myofibroblasts. Moreover, FPR3 phosphorylates IκB to decrease NF-κB inhibition, thereby promoting the synthesis and release of the inflammatory cytokines IL-1β, TNF-α, and IL-6.

Conclusion: FPR3 is a crucial molecule that causes capsular development and contracture following rhinoplasty. In the future, local suppression of FPR3 may be an effective treatment for relieving capsular contracture.