FERMT1 knockdown attenuates inflammation induced by intracerebral hemorrhage in rats via NLRP3/NF- κB pathway

Exp Anim. 2023 Feb 3. doi: 10.1538/expanim.22-0145. Online ahead of print.ABSTRACTIntracerebral hemorrhage (ICH) is an incurable neurological disease. Microglia activation and its related inflammation contribute to ICH-associated brain damage. FERM domain containing kindlin 1 (FERMT1) is an integrin-binding protein that participates in microglia-associated inflammation, but its role in ICH is unclear. An ICH model was constructed by injecting 50 μl of autologous blood into the bregma of rats. FERMT1 siRNA was injected into the right ventricle of the rat for knockdown of FERMT1. A significant striatal hematoma was observed in ICH rats. FERMT1 knockdown reduced the water content of brain tissue, alleviated brain hematoma and improved behavioral function in ICH rats. FERMT1 knockdown reduced microglia activity, inhibited NLR family pyrin domain containing 3 (NLRP3) inflammasome activity and decreased the expression of inflammatory factors including interleukin-1β (IL-1β) and interleukin 18 (IL-18) in the peri-hematoma tissues. BV2 microglial cells were transfected with FERMT1 siRNA and incubated with 60 μM Hemin for 24 h. Activation of NLRP3 inflammasome induced by hemin were reduced in microglia when FERMT1 was knocked down, leading to decreased production of inflammatory factors IL-1β and IL-18. In addition, knockdown of FERMT1 prevented the activation of nuclear factor kappa B (NF-κB) signaling pathway in vivo and in vitro. Our findings suggested that down-regulation of...

Source: Experimental Animals - February 5, 2023 Category: Research Authors: Jianqiang Wei Jing Yin Ying Cui Kaijie Wang Mingyan Hong Jianzhong Cui Source Type: research