title: Epigallocatechin gallate attenuates fibroblast proliferation and excessive collagen production by effectively intervening TGF-β1 signalling.
abstract: Pulmonary fibrosis (PF) poses a huge burden to the patients and society due to lack of an effective treatment drug. Activation of fibrocyte, fibroblast and myofibroblasts are important steps in the development of PF. Targeting this common pathway with natural chemicals may lead to the development of new drug regimens for PF treatment. In this study, PF was induced in male Wistar rats by intratracheal administration of Bleomycin (BLM). Epigallocatechin gallate (EGCG) was administered to one of the groups of rats to test its efficacy against the development of PF. Bleomycin-induction resulted in significant elevation of matrix metalloproteinase (MMP)-2 and -9 expression, increased RNA and protein expression of transforming growth factor (TGF)-β1, Smads and alpha-smooth muscle actin (α-SMA). EGCG treatment normalized the BLM induced aberrations in these rats. The protective role of EGCG was also validated in vitro using the WI-38 fibroblast cell line. TGF-β1 incubated cells exhibited increased fibroblast proliferation and hydroxyproline levels with a concomitant decrease in the expression of MMPs 2 and 9. An increase in protein expression levels of p-Smad, α-SMA and type I collagen (COL1A) was also exhibited by fibroblasts upon TGF-β1 incubation. Simultaneous treatment of EGCG to WI-38 cells significantly decreased these protein expressions alongside normalizing the MMPs expression. The study revealed that EGCG inhibited fibroblast activation and collagen accumulation by inhibiting TGF-β1 signalling and thus can be considered as an effective drug against PF.
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, India.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Sriram
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, India.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Kalayarasan
authors.affiliation: Department of Zoology, University of Madras, Guindy Campus, Chennai, India.
authors.forename: Ramar
authors.initials: R
authors.lastname: Manikandan
authors.affiliation: Department of Zoology, University of Madras, Guindy Campus, Chennai, India.
authors.forename: Munusamy
authors.initials: M
authors.lastname: Arumugam
authors.affiliation: Department of Biochemistry, University of Madras, Guindy Campus, Chennai, India.
authors.forename: Ganapasam
authors.initials: G
authors.lastname: Sudhandiran
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D002392:Catechin; D003094:Collagen; C045651:epigallocatechin gallate; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: EGCG; TGF-β1; collagen; fibroblast; pulmonary fibrosis