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논문분류	춘계학술대회 초록집
제목	Low dose colchicine inhibits the NLRP3 inflammasome activation to protect kidney fibrosis
저자	Ga Young Heo
출판정보	2024; 2024(1):
키워드
초록	Objectives: Chronic kidney disease (CKD) is a progressive disease characterized by renal fibrosis. Recent studies have reported that the NOD-like receptor, pyrin domain containing 3 (NLRP3) inflammasome has emerged as a potential contributor to kidney injury. Colchicine has been shown to suppress NLRP3 inflammasome assembly and the effects of inflammatory cells. However, it remains unknown whether low-dose colchicine can inhibit kidney fibrosis via suppressing the NLRP3 inflammasome pathway. Methods: In vitro, renal tubular epithelial cells (RTECs) were isolated from C57BL/6 mice. Fibrosis markers and NLRP3 inflammasome were examined in RTECs stimulated with TGF-β (10 ng/ml) for 48h with or without treating with colchicine (0.1, 1 uM). In vivo, mice were divided into 4 groups: control without colchicine, control with colchicine, CKD without colchicine, and CKD with colchicine. CKD model was induced by administering an adenine diet. Colchicine groups were treated with colchicine 0.5mg via osmotic pump and were sacrificed after 3 weeks. Bone marrow-derived macrophages (BMDMs) were isolated. Fibrosis markers and NLRP3 inflammasome were examined in tissue and BMDMs. The oligomerization of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-mediated cross-linking assay was performed in BMDMs. Results: In vitro, RTECs stimulated with TGF-β increased the expression of fibrotic and cell injury markers and showed activation of the NLRP3 pathway. After treating with colchicine, NLRP3 inflammasome and fibrotic markers were decreased. In vivo, the activation of the NLRP3 inflammasome and kidney fibrosis were increased in the CKD group mice. However, these were significantly decreased in the CKD with colchicine group. Oligomerization of NLRP3 with ASC was significantly increased in BMDMs from the CKD mice model; while significantly decreased by colchicine treatment. Conclusions: Colchicine attenuated kidney inflammation and fibrosis in a mouse model of adenine-induced kidney injury via inhibiting NLRP3 inflammasome assembly and activation.
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