The Protective Effect of Melittin on Renal Fibrosis in an Animal Model of Unilateral Ureteral Obstruction.

Hyun-Jin An,Sang-Mi Han,Woon-Hae Kim,Kwan-Kyu Park,Jung-Yeon Kim

doi:10.3390/molecules21091137

Abstract

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.

Highlights

Renal fibrosis is the principal pathological process underlying the progression of chronic kidney disease that leads to end-stage renal disease [1]
To investigate the ability of melittin to suppress myofibroblast considered a key process in tubulointerstitial fibrosis, which accounts for the accumulation of the activation, this study examined the expression of α-smooth muscle actin (α-SMA)—a representative marker of activated
The ureteral obstruction (UUO) model is useful for the examination of mechanisms of interstitial fibrosis and

Summary

Introduction

Renal fibrosis is the principal pathological process underlying the progression of chronic kidney disease that leads to end-stage renal disease [1]. Renal fibrosis is the final stage of renal injury that results from various etiologies, such as diabetic nephropathy, hypertensive glomerulosclerosis, and chronic renal allograft nephropathy, among others [3,4]. These processes are characterized by the infiltration of inflammatory cells, interstitial accumulation of fibroblasts, proliferation of myofibroblasts, deposition of the extracellular matrix (ECM), and loss of renal tubule epithelial cells, which collectively lead to end-stage renal failure [5]. Many different types of cytokines and growth factors are involved; tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) play key roles as mediators of renal interstitial fibrosis by regulating ECM production [8]

Methods

Results

Conclusion