Objective and background
The overactivation of NLRP3 inflammasome is a critical factor for ulcerative colitis (UC). We found that heat shock transcription factor 2 (HSF2), which is highly expressed in UC, could inhibit the activation of NLRP3 inflammasome and reduce IL-1β in intestinal epithelial cells(IECs), but the mechanisms were still unclear. We aimed to elucidate the mechanisms of HSF2 inhibiting the activation of NLRP3 inflammasome of IECs.
TEM was used to detect the number of damaged mitochondria and the level of mitophagy in intestinal mucosa of UC patients, healthy controls, mice and Caco-2 cells. ROS levels were detected by immunofluorescence or flow cytometry. RT-PCR, WB and immunohistochemistry were used to detect the level of PARL, PINK1 and Parkin.
The levels of mitophagy and ROS in intestinal mucosa of UC patients were positively correlated with disease activity. In IECs, after downregulation of HSF2, mitophagy reduced and number of damaged mitochondria and ROS increased, while overexpression of HSF2 showed opposite results. In addition, HSF2 might regulate mitophagy through PARL/PINK1/Parkin signaling pathway.
HSF2 may promote mitophagy and decrease the level of mtROS through the PARL/PINK1/Parkin signaling pathway, which might be a potential mechanism of HSF2 inhibiting inflammation in UC.