Daidzein exhibits anti-fibrotic effect by reducing the expressions of Proteinase activated receptor 2 and TGFβ1/smad mediated inflammation and apoptosis in Bleomycin-induced experimental pulmonary fibrosis.
Pulmonary fibrosis (PF) is a progressive lethal disorder. In this study, the effect of daidzein, a soyisoflavone against Bleomycin (BLM) induced PF in rats was elucidated. A single intratracheal instillation of BLM (3 U/kg.bw) was administered in rats to induce PF. Daidzein (0.2 mg/kg) was administered subcutaneously, twice a week for a period of 28 days. Daidzein restored the histological alteration and aberrant collagen deposition, suppressed the mast cells, and reduced the expressions of Cyclooxygenase 2 (COX2) and Nuclear factor kappa B (Nf-kB) in lung tissue of BLM-induced rats. Treatment with daidzein reduced the expression of Matrix metalloproteinase 2 (MMP-2) and increased the expression of Tissue inhibitor of matrixmetalloproteinases 1 (TIMP 1). Recently, Proteinase activated receptor 2 (PAR2) has been reported to play a major role in the progression of PF. Confocal microscopic and immunoblot analysis revealed that BLM injured rat lungs exhibited increased expression of PAR2 that was reduced upon treatment with daidzein. During BLM induction, Transforming growth factor beta (TGFβ1) was found to be up-regulated along with p-smad2/3, a mediator of TGFβ signaling. Further, daidzein regulated the apoptosis by modulating the expressions of Bcl-2, Bax and caspase 3. This study provides evidence on the anti-fibrotic role of daidzein in BLM-induced experimental fibrosis.
Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, India.
Syamala
S
Soumyakrishnan
Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, India.
Thomas
T
Divya
Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, India.
Srinivasan
S
Kalayarasan
Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, India.
Narayanan
N
Sriram
Cell Biology Laboratory, Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, India. Electronic address: sudhandiran@unom.ac.in.
Ganapasam
G
Sudhandiran
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001761:Bleomycin / Q000009:adverse effects; D003094:Collagen / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D044464:Receptor, PAR-2 / Q000378:metabolism*; D051785:Smad Proteins / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D007529:Isoflavones; D044464:Receptor, PAR-2; D051785:Smad Proteins; C508960:TGFB1 protein, human; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; C004742:daidzein; D003094:Collagen; D020778:Matrix Metalloproteinase 2
Apoptosis; Bleomycin; Daidzein; Protease activated receptor 2; Pulmonary fibrosis; Transforming growth factor beta