Characterization and Expression of TGF-β Proteins and Receptor in Sea Cucumber (Holothuria scabra): Insights into Potential Applications via Molecular Docking Predictions

<i>Holothuria scabra</i> has long been acknowledged in traditional medicine for its therapeutic properties. The transforming growth factor-beta (TGF-β) superfamily is crucial in regulating cellular processes, including differentiation, proliferation, and immune responses. This study marks the first exploration of the gene expression localization, sequence conservation, and functional roles of <i>H. scabra</i> TGF-β proteins, specifically activin (<i>Holsc</i>Activin), inhibin (<i>Holsc</i>Inhibin), and the TGF-β receptor (<i>Holsc</i>TGFBR), across various organs. In situ hybridization indicated that <i>Holsc</i>Activin and <i>Holsc</i>Inhibin are expressed in the intestine, respiratory tree, ovary, testis, and inner body wall. This suggests their roles in nutrient absorption, gas exchange, reproduction, and extracellular matrix remodeling. Notably, <i>Holsc</i>TGFBR demonstrated a similar tissue-specific expression pattern, except for its absence in the respiratory tree. Bioinformatics analysis reveals that <i>Holsc</i>TGFBR shares significant sequence similarity with <i>Homsa</i>TGFBR, especially in regions essential for signal transduction and inhibition. Molecular docking results indicate that <i>Holsc</i>Activin may promote receptor activation, while <i>Holsc</i>Inhibin functions as a natural antagonist, reflecting the signaling mechanisms of human TGF-β proteins. Interestingly, cross-species ternary complex docking with human TGF-β receptors further supports these findings, showing that <i>Holsc</i>Activin moderately engages the receptors, whereas <i>Holsc</i>Inhibin exhibits strong binding, suggestive of competitive inhibition. These results indicate that <i>H. scabra</i> TGF-β proteins retain the structural and functional features of vertebrate TGF-β ligands, supporting their potential applications as natural modulators in therapeutic and functional food development.