Inflammatory Signaling\nvia PEIZO1 Engages and Enhances\nthe LPS-Mediated Apoptosis during Clinical Mastitis

Bovine clinical mastitis is characterized\nby inflammation\nand immune\nresponses, with apoptosis of mammary epithelial cells as a cellular\nreaction to infection. PIEZO1, identified as a mechanotransduction\neffector channel in nonruminant animals and sensitive to both mechanical\nstimuli or inflammatory signals like lipopolysaccharide (LPS). However,\nits role in inflammatory processes in cattle has not been well-documented.\nThe aim of this study was to elucidate the in situ expression of PIEZO1\nin bovine mammary gland and its potential involvement in clinical\nmastitis. We observed widespread distribution and upregulation of\nPIEZO1 in mammary epithelial cells in clinical mastitis cows and LPS-induced\nmouse models, indicating a conserved role across species. In vitro\nstudies using mammary epithelial cells (MAC-T) revealed that LPS upregulates\nPIEZO1. Notably, the effects of PIEZO1 artificial activator Yoda1\nincreased apoptosis and NLRP3 expression, effects mitigated by PIEZO1\nsilencing or NLRP3 inhibition. In conclusion, the activation of the\nPIEZO1-NLRP3 pathway induces abnormal apoptosis in mammary epithelial\ncells, potentially serving as a regulatory mechanism to combat inflammatory\nresponses to abnormal stimuli.