The Protective Effect of Melittin on Renal Fibrosis in an Animal Model of Unilateral Ureteral Obstruction.
Renal fibrosis is the principal pathological process underlying the progression of chronic kidney disease that leads to end-stage renal disease. Melittin is a major component of bee venom, and it has anti-bacterial, anti-viral, and anti-inflammatory properties in various cell types. Thus, this study examined the therapeutic effects of melittin on the progression of renal fibrosis using the unilateral ureteral obstruction (UUO) model. In addition, the effects of melittin on inflammation and fibrosis in renal fibroblast cells were explored using transforming growth factor-β1 (TGF-β1). Histological observation revealed that UUO induced a considerable increase in the number of infiltrated inflammatory cells. However, melittin treatment markedly reduced these reactions compared with untreated UUO mice. The expression levels of inflammatory cytokines and pro-fibrotic genes were significantly reduced in melittin-treated mice compared with UUO mice. Melittin also effectively inhibited fibrosis-related gene expression in renal fibroblasts NRK-49F cells. These findings suggest that melittin attenuates renal fibrosis and reduces inflammatory responses by the suppression of multiple growth factor-mediated pro-fibrotic genes. In conclusion, melittin may be a useful therapeutic agent for the prevention of fibrosis that characterizes the progression of chronic kidney disease.
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. ahj119@cu.ac.kr.
Hyun-Jin
HJ
An
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. jy1118@cu.ac.kr.
Jung-Yeon
JY
Kim
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. kimwoonhae@cu.ac.kr.
Woon-Hae
WH
Kim
Deparment of Agricultural Biology, National Academy of Agricultural Science, RDA, 300, Nongsaengmyeong-ro, Wansan-gu, Jeonju 54875, Korea. sangmih@korea.kr.
Sang-Mi
SM
Han
Department of Pathology, College of Medicine, Catholic University of Daegu, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. kkpark@cu.ac.kr.
Kwan-Kyu
KK
Park
D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008555:Melitten / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014517:Ureteral Obstruction / Q000378:metabolism / Q000517:prevention & control*
C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D008555:Melitten
UUO; inflammation; melittin; renal fibrosis