대한신장학회

논문분류	춘계학술대회 초록집
제목	Sulfatide-selective NKT cells mediate M2 to M1 polarization resulting in amelioration of kidney fibrosis.
저자	*Seung hee YANG1, Sunhwa LEE1, Mi-yeon YU2, Yong chul KIM2, Seung seok HAN2, Hajeong LEE2, Jung pyo LEE3, Ran hui CHA4, Dong ki KIM2, Yon su KIM2
출판정보	2017; 2017(1):
키워드	Chronic Kidney Disease, Kidney Fibrosis, Myofibroblast, Macrophage-myofibroblast transition (MMT), Natural Killer T cell
초록	Objectives : Macrophage subtype polarization has been suggested as a key player related to kidney fibrosis. Moreover, myofibroblast is originated from macrophage so-called by means of macrophage-myofibroblast transition (MMT). We investigated its phenotypic skewing of these cells by sulfatide selective type II NKT cells and its impact on kidney fibrosis. Methods : To elucidate the impact of activated type II NKT cells on phenotypic switch of M1/M2 macrophages and interstitial fibrosis, sulfatide-selective NKT II cells from B6.Jα281-/- mice were isolated, and co-cultured with primary cultured proximal epithelial cells. In addition, for in vivo study, sulfatide was injected one hour before unilateral ureteral obstruction (UUO) operation to B6 mouse. Subsequently, total cellular RNA was extracted from minced kidney, lymph nodes, and fresh blood to analyze changes in transcript expression levels using quantitative real-time PCR and microarray. Furthermore, the proportion of infiltrated αSMA+/CD206+ double positive cells in UUO kidney was compared according to application of sulfatide. Results : Severity of renal fibrosis and the proportion of αSMA+/CD206+ double positive cells was attenuated after sulfatide injection. At the same time, sulfatide reduced senescence, shown by decreased levels of SA-β-Gal. Sulfatide stimulated polarization from M2 to M1 accompanying by increased iNOS, STAT1, SOCS3 and decreased arginase, STAT3. Pro-fibrotic transcripts, fibronectin and TGFβ, was decreased by adding sulfatide-selective NKT. Moreover, the expression level of NGAL and IL-1β, a marker of kidney damage and inflammation, was attenuated. At the same time, diminution of immunologic transcripts such as CD44, CCL5, CCL9, and macrophage mannose receptor 1 was also observed. Conclusions : Sulfatide-selective NKT cell mediates macrophage polarization skewing from M2 to M1 macrophage via switching on STAT1 resulting in ameliorating renal fibrosis. Infiltration of myofibroblast cells co-expressing M2 marker are also decreased by sulfatide accompanying by reduced fibrosis. Inducing the polarization of macrophages by modulation of NKT cells can be suggested as therapeutic target for curbing fibrosis.
원문(PDF)	PDF 원문보기

간행물 검색

대한신장학회 회원관리 규정