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: Su-Hyun Park, Hyun-Ji Cho, Yun-Jeong Jeong, Jae-Moon Shin, Jeong-Han Kang, Kwan-Kyu Park, Jung-Yoon Choe, Yoon-Yub Park, Young-Seuk Bae, Sang-Mi Han, Sung-Kwon Moon, Wun-Jae Kim, Yung Hyun Choi, Young-Chae Chang
• Journal: The American journal of Chinese medicine (Am J Chin Med) Vol. 42 Issue 5 Pg. 1139-52 ( 2014) ISSN: 1793-6853 [Electronic] Singapore
• PMID: 25178280 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bee Venoms
• Collagen Type I
• Fibronectins
• Plasminogen Activator Inhibitor 1
• Receptors, Transforming Growth Factor beta
• Smad Proteins
• Transforming Growth Factor beta
• Melitten
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type II

Topics

• Animals
• Bee Venoms (pharmacology)
• Cells, Cultured
• Collagen Type I (genetics, metabolism)
• Depression, Chemical
• Fibroblasts (pathology)
• Fibronectins (genetics, metabolism)
• Fibrosis
• Gene Expression (drug effects, genetics)
• Kidney (cytology, pathology)
• Kidney Diseases (drug therapy, pathology)
• MAP Kinase Signaling System (drug effects, genetics)
• Melitten (pharmacology, therapeutic use)
• Phosphorylation (drug effects)
• Plasminogen Activator Inhibitor 1 (genetics, metabolism)
• Protein Serine-Threonine Kinases (metabolism)
• Rats
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (metabolism)
• Signal Transduction (drug effects, genetics)
• Smad Proteins (metabolism)
• Transforming Growth Factor beta (antagonists & inhibitors)