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Title: Induction of galectin-1 by TGF-β1 accelerates fibrosis through enhancing nuclear retention of Smad2

Fibrosis is one of the most serious side effects in cancer patients undergoing radio-/ chemo-therapy, especially of the lung, pancreas or kidney. Based on our previous finding that galectin-1 (Gal-1) was significantly increased during radiation-induced lung fibrosis in areas of pulmonary fibrosis, we herein clarified the roles and action mechanisms of Gal-1 during fibrosis. Our results revealed that treatment with TGF-β1 induced the differentiation of fibroblast cell lines (NIH3T3 and IMR-90) to myofibroblasts, as evidenced by increased expression of the fibrotic markers smooth muscle actin-alpha (α-SMA), fibronectin, and collagen (Col-1). We also observed marked and time-dependent increases in the expression level and nuclear accumulation of Gal-1. The TGF-β1-induced increases in Gal-1, α-SMA and Col-1 were decreased by inhibitors of PI3-kinase and p38 MAPK, but not ERK. Gal-1 knockdown using shRNA decreased the phosphorylation and nuclear retention of Smad2, preventing the differentiation of fibroblasts. Gal-1 interacted with Smad2 and phosphorylated Smad2, which may accelerate fibrotic processes. In addition, up-regulation of Gal-1 expression was demonstrated in a bleomycin (BLM)-induced mouse model of lung fibrosis in vivo. Together, our results indicate that Gal-1 may promote the TGF-β1-induced differentiation of fibroblasts by sustaining nuclear localization of Smad2, and could be a potential target formore » the treatment of pulmonary fibrotic diseases. - Highlights: • Galectin-1 (Gal-1) promotes TGF-β-induced fibroblast differentiation via activation of PI3-kinase and p38 MAPK. • Gal-1 binds to Smad2 and phosphorylated Smad2. • GAl-1 may be a new therapeutic target for attenuating lung fibrotic process.« less
Authors:
;  [1] ;  [2] ; ; ;  [1] ;  [3] ;  [4] ;  [2] ;  [5] ;  [1]
  1. Division of Radiation Cancer Sciences, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)
  2. Department of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)
  3. Department of Applied Bioscience, CHA University (Korea, Republic of)
  4. Department of Biochemistry and Molecular Biology, Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)
  5. Division of Biological Science, Sookmyung Women's University, Seoul 140-742 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22416916
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 326; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTIN; BLEOMYCIN; COLLAGEN; FIBROBLASTS; FIBROSIS; GROWTH FACTORS; IN VIVO; KIDNEYS; LUNGS; MICE; MUSCLES; NEOPLASMS; PANCREAS; PHOSPHORYLATION; RETENTION; SIDE EFFECTS; THERAPY; TIME DEPENDENCE