miR-325-3p targets GSDMD in macrophages to attenuate lung injury induced by Streptococcus equi subsp. zooepidemicus.

Streptococcus equi subsp. zooepidemicus (SEZ) primarily functions as a zoonotic pathogen, with the capacity to infect a wide variety of animal species, including humans. The present study has captured the importance role of GSDMD in mice against SEZ, here, with the help of published works, we chose miR-325-3p as a regulator to GSDMD and investigated the role of miR-325-3p during SEZ infection in vitro and vivo. In this study, SEZ significantly increased the expression of GSDMD and release of cytokines in macrophages. Both prediction assay using Target Scan databases and luciferase reporter assay showed that miR-325-3p directly targeted to GSDMD. Moreover, overexpression of miR-325-3p significantly decreased the expression of GSDMD and the release of IL-1β and IL-18 in macrophages infected with SEZ. And inhibition of miR-325-3p expression exhibited the opposite effect. In vivo experiments, we found that injection of miR-325-3p mimics into mice alleviated lung injury induced with SEZ, and miR-325-3p mimics also reduced the IL-1β and IL-18 contents in bronchoalveolar lavage fluid (BALF) and bacterial loads in lung tissue. Results in this study revealed that miR-325-3p suppressed inflammatory response triggered by SEZ both in vitro and vivo. Taken together, our findings provided evidence to identify miR-325-3p as a potential therapeutic agent to SEZ infection.