Discoidin domain receptor (DDR)2 mediates constitutive and collagen I-induced migration of primary human lung fibroblasts through collagen IV
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Ruiz, Pedro and Jarai, Gabor (2012) Discoidin domain receptor (DDR)2 mediates constitutive and collagen I-induced migration of primary human lung fibroblasts through collagen IV. Fibrogenesis and Tissue Repair, 5 (3). ISSN 1755-1536
Abstract
Discoidin domain receptors (DDRs), DDR1 and DDR2, are receptor tyrosine kinases (RTKs) with the unique ability among RTKs to respond to collagen. DDRs have been reported to induce the expression of various pro-inflammatory and pro-fibrotic genes including matrix metalloproteinases (MMPs). We have previously shown that collagen I induces DDR1 and MMP-10 through DDR2 activation and a janus kinase (JAK)2 and extracellular signal-regulated kinase (ERK)1/2-mediated mechanism in primary human lung fibroblasts (NHLFs) suggesting that these signalling pathways play a role in fibroblast function. Fibroblasts can traverse basement membrane barriers during development, wound healing and pathological conditions such as cancer and fibrosis by activating tissue-invasive programs, the identity of which remain largely undefined. In the present work we investigated the role of DDRs and DDR-associated signal transduction in these processes. Our data show that DDR2, but not DDR1 is essential for fibroblast proliferation and invasion of collagen I, whereas constitutive and collagen I-induced fibroblast migration through collagen IV is DDR1, DDR2, JAK2 and ERK1/2-dependent. Our data provide new insights into the role of DDRs in fibroblast proliferation and their ability to migrate trough extracellular matrix (ECM) components.
| Item Type: | Article |
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| Date Deposited: | 13 Oct 2015 13:15 |
| Last Modified: | 13 Oct 2015 13:15 |
| URI: | https://oak.novartis.com/id/eprint/5747 |