tailieunhanh - Báo cáo khoa học: a-Defensins increase lung fibroblast proliferation and collagen synthesis via the b-catenin signaling pathway

a-defensins are released from granules of leukocytes and are implicated in inflammatory and fibrotic lung diseases. In the present study, the effects of a-defensins on the proliferation and collagen synthesis of lung fibroblasts were examined. We found thata-defensin-1 and a-defensin-2 induced dose-dependent increases in the incorporation of 5-bromo-2¢-deoxy-uridine into newly synthesized DNA in two lines of human lung fibroblasts (HFL-1 and LL-86) | a-Defensins increase lung fibroblast proliferation and collagen synthesis via the b-catenin signaling pathway Weihong Han1 Wei Wang2 Kamal A. Mohammed2 3 and Yunchao Su1 4 5 6 1 Department of Pharmacology and Toxicology MedicalCollege of Georgia Augusta GA USA 2 Department of Medicine University of Florida College of Medicine Gainesville FL USA 3 Research Service Malcom RandallVA MedicalCenter Gainesville FL USA 4 Center for Biotechnology and Genomic Medicine MedicalCollege of Georgia Augusta GA USA 5 Vascular Biology Center MedicalCollege of Georgia Augusta GA USA 6 Department of Medicine MedicalCollege of Georgia Augusta GA USA Keywords b-catenin collagen defensins fibroblasts proliferation Correspondence Y. Su Department of Pharmacology and Toxicology MedicalCollege of Georgia 1120 15th Street Augusta GA 30912 USA Fax 1 706 721 2347 Tel 1 706 721 7641 E-mail ysu@ Received 28 May 2009 revised 9 August 2009 accepted 10 September 2009 doi a-defensins are released from granules of leukocytes and are implicated in inflammatory and fibrotic lung diseases. In the present study the effects of a-defensins on the proliferation and collagen synthesis of lung fibroblasts were examined. We found that a-defensin-1 and a-defensin-2 induced dosedependent increases in the incorporation of 5-bromo-2 -deoxy-uridine into newly synthesized DNA in two lines of human lung fibroblasts HFL-1 and LL-86 suggesting that a-defensin-1 and a-defensin-2 stimulate the proliferation of lung fibroblasts. a-defensin-1 and a-defensin-2 also increased collagen-I mRNA COL1A1 levels and protein contents of colla-gen-I and active dephosphorylated b-catenin without changes in total b-catenin protein content in lung fibroblasts HFL-1 and LL-86 . Inhibition of the b-catenin signaling pathway using quercetin prevented increases in cell proliferation and the protein content of collagen-I and active dephos-phorylated b-catenin in lung fibroblasts and in COL1A1 mRNA .