WITHDRAWN: RNA binding protein Musashi2 regulates dairy cows' mastitis by activating the TGFβ signaling pathway

Abstract

Bacteria-induced mastitis decreased milk production and quality in cows. Persistent inflammation induces epithelial-mesenchymal transition (EMT) in mammary epithelial cells, disrupting tight junctions and losing the immunity of the blood-milk barrier. Maintenance of the blood-milk barrier and reducing the negative effects of inflammation is a challenge. The mouse model and bovine mammary epithelial cells (BMECs) were used to establish mastitis models. Exploring the molecular mechanisms of the RNA-binding protein Musashi2 (Msi2) in mastitis. The results showed that Msi2 regulates the inflammatory response and the blood-milk barrier in mastitis. We found that Msi2 expression was upregulated during mastitis. In LPS-induced BMECs and mice, elevated Msi2 was accompanied by an increase in inflammatory factors and a decrease in tight junction proteins. Silencing of Msi2 alleviated the above indicators induced by LPS. Transcriptional profiling revealed that Msi2 silencing activated the transforming growth factor β (TGFβ) signaling pathway. RNA-interacting protein immunoprecipitation experiments showed that Msi2 could bind transforming growth factor β receptor 1 (TGFβ R1) and affect its mRNA translation, thereby affecting the TGFβ signaling pathway. These results suggest that in mastitis, Msi2 modulates the TGFβ signaling pathway by binding to TGFβR1, inhibits the inflammatory response, and repairs the blood-milk barrier, mitigating the negative effects of mastitis. Msi2 may be a potential target for the treatment of mastitis.