Increased levels of
long noncoding RNA H19 (H19) have been observed in many inflammatory and organ
fibrosis diseases including
ulcerative colitis,
osteoarthritis,
liver fibrosis, renal
fibrosis and
pulmonary fibrosis. However, the role of H19 in
bovine mastitis and
mastitis-caused
fibrosis is still unclear. In our study, H19 was characterized as a novel regulator of EMT induced by transforming growth factor-β1 (TGF-β1) in bovine mammary alveolar cell-T (MAC-T) cell line. We found that H19 was highly expressed in
bovine mastitis tissues and inflammatory MAC-T cells induced by
virulence factors of pathogens. TGF-β1 was also highly expressed in inflammatory MAC-T cells, and exogenous TGF-β1 could induce EMT, enhance
extracellular matrix protein expression, and upregulate H19 expression in epithelial cells. Stable expression of H19 significantly promotes EMT progression and expression of ECM
protein induced by TGF-β1 in MAC-T cells. Furthermore, by using a specific inhibitor of the PI3K/AKT pathway, we demonstrated that TGF-β1 upregulated H19 expression through PI3K/AKT pathway. All these observations imply that the
lncRNA H19 modulated TGF-β1-induced epithelial to mesenchymal transition in bovine epithelial cells through PI3K/AKT signaling pathway, which suggests that mammary epithelial cells might be one source for myofibroblasts in vivo in the mammary glands under an inflammatory condition, thereby contributing to mammary gland
fibrosis.