Knockout of the <i>C4BPA</i> Gene Promotes Mitophagy via Activation of the Pink1/Parkin Pathway and Alleviates the Inflammatory Response by Inhibiting the NF-κB Signalling Pathway in Bovine Mammary Epithelial Cells

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Mastitis is a prevalent disease in the dairy cattle industry and has adverse effects on dairy cows' health and milk quality. Importantly, mastitis is associated with the inflammatory response and mitophagy. As a complement-regulatory factor, C4b-binding protein alpha (C4BPA) has been shown to modulate inflammatory factors. This study further investigates its role and mechanisms in regulating mitophagy and inflammatory responses. Following C4BPA knockout, bovine mammary epithelial cells (BMECs) exhibited reduced expression of TLR4 and key pro-inflammatory cytokines, namely the tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Electron microscopy revealed a marked increase in mitochondrial membrane rupture, as well as cristae disorder and damage and increased reactive oxygen species (ROS) levels. Moreover, Pink1 and Parkin protein levels were increased, as was LC3B lipidation (LC3B-II), whereas p62 protein expression was significantly downregulated. Immunofluorescence indicated substantially increased LC3 colocalization with mitochondria, suggesting that C4BPA gene knockout activated Pink1/Parkin-mediated mitophagy. The fact that C4BPA knockout decreased the levels of p-IκB and p-p65 while increasing those of IκBα and p65 therefore indicates its regulatory role in the NF-κB-mediated inflammatory response. Together, these findings reveal that C4BP

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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