title: Gliotoxin from Aspergillus fumigatus reverses epithelial to mesenchymal transition: implications in renal fibrosis.
abstract: Fibrosis is generally characterized by an excessive accumulation and deposition of extracellular matrix (ECM) that progressively leads to the destruction of functional nephrons of the kidney. Current study is aimed to propose a probable antifibrotic mechanism of gliotoxin, isolated from marine Aspergillus fumigatus strain, in proximal tubule renal epithelial cells by inhibiting HIF-1α, Ang-II and NF-κB in a dose dependent manner. GTX at a concentration of 1.6 ng/ml also showed more than 80% cell viability. Scanning Electron Microscopy, fluorescence microscopy, FACS, mRNA and protein profiles further confirmed that gliotoxin reverses the epithelial to mesenchymal transition in HK-2 cells by scavenging the production of reactive oxygen species (g=69.7) when compared to negative control (g=467.74). Under the light of obtained results, the present study holds immense promise for the biomedical implication of the fungal metabolite, Gliotoxin in medicine for treating various clinical cases of renal fibrosis.
authors.affiliation: Centre for Cellular and Molecular Biology, Hyderabad 500007, India. Electronic address: ira@ccmb.res.in.
authors.forename: Ira
authors.initials: I
authors.lastname: Bhatnagar
authors.affiliation: Department of Marine Bio Convergence Science, Specialized Graduate School Science and Technology Convergence, Pukyong National University, Busan 608-737, Republic of Korea. Electronic address: sknkim@pknu.ac.kr.
authors.forename: Se-Kwon
authors.initials: SK
authors.lastname: Kim
mesh_terms: D001228:Aspergillosis / Q000382:microbiology / Q000473:pathology*; D001232:Aspergillus fumigatus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D005355:Fibrosis / Q000473:pathology; D016166:Free Radical Scavengers / Q000378:metabolism; D005912:Gliotoxin / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000473:pathology*; D008648:Mesoderm / Q000187:drug effects* / Q000502:physiology; D008969:Molecular Sequence Data; D017382:Reactive Oxygen Species / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D004271:DNA, Fungal; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D005912:Gliotoxin
keywords: Epithelial–mesenchymal transition; Gliotoxin; HK-2; Kidney; ROS; Renal fibrosis