Genome-wide characterization and immune-modulatory roles of PPAR genes in Cynoglossus semilaevis: insights into inflammation regulation and host defense

Abstract

Peroxisome proliferator-activated receptors (PPARs), members of the nuclear receptor superfamily, play essential roles in orchestrating metabolic processes and modulating innate immune responses. However, the roles of PPAR genes in Cynoglossus semilaevis remain largely unexplored. In this study, four PPAR genes were identified and categorized into three subfamilies based on genome-wide analysis. Physicochemical property analysis revealed that PPARγ is distinct from the other three isoforms, as it harbors a unique PPARγ_N superfamily domain and is exclusively localized in the nucleus. Comparative and evolutionary analyses demonstrated a high degree of conservation between C. semilaevis and other bony fish. The Ka/Ks ratio consistently remained below 1, suggesting strong purifying selection acting on PPAR genes. qRT-PCR analysis demonstrated a general downregulation of PPARs in the early phase of Vibrio anguillarum infection across multiple tissues, potentially facilitating an inflammatory response against the pathogen. In the later stage, their expression increased, which may play a role in suppressing excessive inflammation. Functional assays demonstrated that overexpression of pparαa, pparδ, and pparγ suppressed LPS-induced exaggerated expression of inflammatory factors, suggesting their roles in negative regulation of excessive immune response. Moreover, protein-protein interaction (PPI) network analysis predicted candidate interactors, offering new avenues for further functional investigation. Collectively, the study provided a comprehensive characterization, expression, and immune function of PPAR genes in Chinese tongue sole, setting a solid foundation for further functional studies and practical usage in disease control.