title: Melittin inhibits TGF-β-induced pro-fibrotic gene expression through the suppression of the TGFβRII-Smad, ERK1/2 and JNK-mediated signaling pathway.
abstract: Renal fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) proteins such as type I collagen, fibronectin, and by the increased expression of PAI-1. This study evaluated the anti-fibrotic effect of bee venom and its major compounds (melittin and apamin) on TGF-β-induced pro-fibrotic gene expression. Bee venom and melittin significantly suppressed type I collagen, fibronectin, and PAI-1 protein expression in the TGF-β-treated kidney fibroblast. However, apamin only inhibited the expression of fibronectin and type I collagen. These results indicated that the inhibitory effects of bee venom on TGF-β-induced pro-fibrotic gene expression are caused by melittin. Moreover, we attempted to elucidate mechanisms underlying the anti-fibrotic effect of melittin. Melittin dramatically inhibited the phosphorylation of TGFβRII and Smad2/3. Also, melittin inhibited the phosphorylation of ERK1/2 and JNK, but not the phosphorylation of PI3K, Akt, and p38. These results suggested that melittin inhibits TGF-β-induced pro-fibrotic genes expression through the suppression of TGFβR-Smad2/3, ERK1/2, and JNK phosphorylation, and melittin can be used as a clinical drug for the treatment of fibrosis associated with renal diseases.
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Cho
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Jeong
authors.forename: Jae-Moon
authors.initials: JM
authors.lastname: Shin
authors.forename: Jeong-Han
authors.initials: JH
authors.lastname: Kang
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Choe
authors.forename: Yoon-Yub
authors.initials: YY
authors.lastname: Park
authors.forename: Young-Seuk
authors.initials: YS
authors.lastname: Bae
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Han
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
mesh_terms: D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism*; D003864:Depression, Chemical; D005347:Fibroblasts / Q000473:pathology*; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism*; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics*; D007668:Kidney / Q000166:cytology / Q000473:pathology*; D007674:Kidney Diseases / Q000188:drug therapy / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics*; D008555:Melitten / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics*; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D001514:Bee Venoms; D024042:Collagen Type I; D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D008555:Melitten; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: Bee Venom; Melittin; Pro-Fibrotic Factor; Renal Fibrosis; Transforming Growth Factor-β