Work

Role of timp2 in Ctenopharyngodon idellus muscle collagen deposition and the regulatory mechanism by Cu2+

Year: 2025

Type: article

Abstract: Collagen serves as one of determinants of fish muscle quality. Timp2 is a key enzyme in collagen metabolism. Its role in grass carp ( Ctenopharyngodon idellus ) and related nutritional regulation mechanism are unknown. Given the important role of copper as a micronutrient in collagen biosynthesis, it was hypothesized that Cu 2+ up-regulates timp2 expression through the TGFβ/Smads signaling pathway, thus modulating grass carp collagen content. In the present study, this hypothesis validation was performed through parallel experiments using the TGF-β/Smads inhibitor SB431542 and timp2 -specific siRNA (si timp2 ) in cultured fibroblasts. Results showed that both si timp2 and SB431542 treatment decreased the collagen content (to 90.2 % ± 0.52 % and 61.8 % ± 1.59 % of control, respectively), down-regulated timp2 expression (by 53.8 % ± 1.30 % and 11.3 % ± 1.91 % relative to control) and up-regulated mmp2 expression (by 33.1 % ± 9.70 % and 10.9 % ± 2.51 % relative to control). Additionally, SB431542 inhibited the TGFβ/Smads signaling pathway ( P < 0.05). Coversely, Cu 2+ supplementation significantly increased the collagen content, up-regulated timp2 expression and enhanced TGFβ/Smads signaling pathway activity, while simultaneously suppressing mmp2 expression ( P < 0.05). Futhermore, after si timp2 or SB431542 treatment, 10 μM Cu 2+ reversed the changes in the relevant indicators induced by both si timp2 and SB431542 treatment ( P < 0.05). These results confirmed the hypothesis that Cu 2+ enhanced collagen deposition through TGFβ/Smads-mediated up-regulation of timp2 . The present study provided novel mechanistic insights into copper-dependent collagen regulation and suggested that dietary copper supplementation could be a practical nutritional strategy to improve muscle texture and product quality in farmed grass carp.

Source: Food Chemistry Molecular Sciences

DOI: 10.1016/j.fochms.2025.100306