Discoidin domain receptors regulate the migration of primary human lung fibroblasts through collagen matrices
Tóm tắt
The two discoidin domain receptors (DDRs), DDR1 and DDR2 are receptor tyrosine kinases (RTKs) with the unique ability among RTKs to respond to collagen. We have previously shown that collagen I induces DDR1 and matrix metalloproteinase (MMP)-10 expression through DDR2 activation and a Janus kinase (JAK)2 and extracellular signal-regulated kinase (ERK)1/2-mediated mechanism in primary human lung fibroblasts suggesting that these signaling 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. Transwell migration experiments showed that normal human lung fibroblast (NHLF) transmigration through collagen I-coated inserts is mediated by DDR2 and the DDR2-associated signaling kinases JAK2 and ERK1/2, but not DDR1. Additionally, experiments with specific small interfering (si)RNAs revealed that collagen I-induced expression of MMP-10 and MMP-2 is DDR2 but not DDR1 dependent in NHLFs. Our data showed that collagen I increases NHLF migration through collagen IV, the main component of basement membranes. Furthermore, basal and collagen I-induced NHLF migration through collagen IV-coated inserts was both DDR2 and DDR1 dependent. Finally, DDR2, but not DDR1 was shown to be involved in fibroblast proliferation. Our results suggest a mechanism by which the presence of collagen I in situations of excessive matrix deposition could induce fibroblast migration through basement membranes through DDR2 activation and subsequent DDR1 and MMP-2 gene expression. This work provides new insights into the role of DDRs in fibroblast function.
Tài liệu tham khảo
Vogel WF, Abdulhussein R, Ford CE: Sensing extracellular matrix: an update on discoidin domain receptor function. Cell Signal. 2006, 18: 1108-1116. 10.1016/j.cellsig.2006.02.012.
Labrador JP, Azcoitia V, Tuckermann J, Lin C, Olaso E, Manes S, Bruckner K, Goergen JL, Lemke G, Yancopoulos G, Angel P, Martinez C, Klein R: The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism. EMBO Rep. 2001, 2: 446-452.
Vogel W, Gish GD, Alves F, Pawson T: The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell. 1997, 1: 13-23. 10.1016/S1097-2765(00)80003-9.
Gelse K, Poschl E, Aigner T: Collagens--structure, function, and biosynthesis. Adv Drug Deliv Rev. 2003, 55: 1531-1546. 10.1016/j.addr.2003.08.002.
Hou G, Vogel WF, Bendeck MP: Tyrosine kinase activity of discoidin domain receptor 1 is necessary for smooth muscle cell migration and matrix metalloproteinase expression. Circ Res. 2002, 90: 1147-1149. 10.1161/01.RES.0000022166.74073.F8.
Faraci E, Eck M, Gerstmayer B, Bosio A, Vogel WF: An extracellular matrix-specific microarray allowed the identification of target genes downstream of discoidin domain receptors. Matrix Biol. 2003, 22: 373-381. 10.1016/S0945-053X(03)00053-2.
Olaso E, Labrador JP, Wang L, Ikeda K, Eng FJ, Klein R, Lovett DH, Lin HC, Friedman SL: Discoidin domain receptor 2 regulates fibroblast proliferation and migration through the extracellular matrix in association with transcriptional activation of matrix metalloproteinase-2. J Biol Chem. 2002, 277: 3606-3613. 10.1074/jbc.M107571200.
Das S, Ongusaha PP, Yang YS, Park JM, Aaronson SA, Lee SW: Discoidin domain receptor 1 receptor tyrosine kinase induces cyclooxygenase-2 and promotes chemoresistance through nuclear factor-kappaB pathway activation. Cancer Res. 2006, 66: 8123-8130. 10.1158/0008-5472.CAN-06-1215.
Chin GS, Lee S, Hsu M, Liu W, Kim WJ, Levinson H, Longaker MT: Discoidin domain receptors and their ligand, collagen, are temporally regulated in fetal rat fibroblasts in vitro. Plast Reconstr Surg. 2001, 107: 769-776. 10.1097/00006534-200103000-00018.
Olaso E, Ikeda K, Eng FJ, Xu L, Wang LH, Lin HC, Friedman SL: DDR2 receptor promotes MMP-2-mediated proliferation and invasion by hepatic stellate cells. J Clin Invest. 2001, 108: 1369-1378.
Ferri N, Carragher NO, Raines EW: Role of discoidin domain receptors 1 and 2 in human smooth muscle cell-mediated collagen remodeling: potential implications in atherosclerosis and lymphangioleiomyomatosis. Am J Pathol. 2004, 164: 1575-1585. 10.1016/S0002-9440(10)63716-9.
Heinzelmann-Schwarz VA, Gardiner-Garden M, Henshall SM, Scurry J, Scolyer RA, Davies MJ, Heinzelmann M, Kalish LH, Bali A, Kench JG, Edwards LS, Vanden Bergh PM, Hacker NF, Sutherland RL, O'Brien PM: Overexpression of the cell adhesion molecules DDR1, Claudin 3, and Ep-CAM in metaplastic ovarian epithelium and ovarian cancer. Clin Cancer Res. 2004, 10: 24427-24436.
Balduino A, Hurtado SP, Frazao P, Takiya CM, Alves LM, Nasciutti LE, El-Cheikh MC, Borojevic R: Bone marrow subendosteal microenvironment harbours functionally distinct haemosupportive stromal cell populations. Cell Tissue Res. 2005, 319: 255-266. 10.1007/s00441-004-1006-3.
Avivi-Green C, Singal M, Vogel WF: Discoidin domain receptor 1-deficient mice are resistant to bleomycin-induced lung fibrosis. Am J Respir Crit Care Med. 2006, 174: 420-427. 10.1164/rccm.200603-333OC.
Xu J, Lamouille S, Derynck R: TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 2009, 19: 156-172. 10.1038/cr.2009.5.
Ongusaha PP, Kim JI, Fang L, Wong TW, Yancopoulos GD, Aaronson SA, Lee SW: p53 induction and activation of DDR1 kinase counteract p53-mediated apoptosis and influence p53 regulation through a positive feedback loop. Embo J. 2003, 22: 1289-1301. 10.1093/emboj/cdg129.
Coward WR, Saini G, Jenkins G: The pathogenesis of idiopathic pulmonary fibrosis. Ther Adv Respir Dis. 2010, 4: 367-388. 10.1177/1753465810379801.
Benbow U, Schoenermark MP, Mitchell TI, Rutter JL, Shimokawa K, Nagase H, Brinckerhoff CE: A novel host/tumor cell interaction activates matrix metalloproteinase 1 and mediates invasion through type I collagen. J Biol Chem. 1999, 274: 25371-25378. 10.1074/jbc.274.36.25371.
Ruiz PA, Jarai G: Collagen I induces discoidin domain receptor (DDR) 1 expression through DDR2 and a JAK2-ERK1/2-mediated mechanism in primary human lung fibroblasts. J Biol Chem. 2011, 286: 12912-12923. 10.1074/jbc.M110.143693.
Chandler S, Miller KM, Clements JM, Lury J, Corkill D, Anthony DC, Adams SE, Gearing AJ: Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview. J Neuroimmunol. 1997, 72: 155-161. 10.1016/S0165-5728(96)00179-8.
Murphy G, Cockett MI, Ward RV, Docherty AJ: Matrix metalloproteinase degradation of elastin, type IV collagen and proteoglycan. A quantitative comparison of the activities of 95 kDa and 72 kDa gelatinases, stromelysins-1 and -2 and punctuated metalloproteinase (PUMP). Biochem J. 1991, 277: 277-279.
Rechardt O, Elomaa O, Vaalamo M, Paakkonen K, Jahkola T, Hook-Nikanne J, Hembry RM, Hakkinen L, Kere J, Saarialho-Kere U: Stromelysin-2 is upregulated during normal wound repair and is induced by cytokines. J Invest Dermatol. 2000, 115: 778-787. 10.1046/j.1523-1747.2000.00135.x.
Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T: Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem. 2003, 253: 269-285. 10.1023/A:1026028303196.
Choi M, Cho WS, Han BS, Cho M, Kim SY, Yi JY, Ahn B, Kim SH, Jeong J: Transient pulmonary fibrogenic effect induced by intratracheal instillation of ultrafine amorphous silica in A/J mice. Toxicol Lett. 2008, 182: 97-101. 10.1016/j.toxlet.2008.08.019.
Leitinger B, Hohenester E: Mammalian collagen receptors. Matrix Biol. 2007, 26: 146-155. 10.1016/j.matbio.2006.10.007.
Van Agtmael T, Bruckner-Tuderman L: Basement membranes and human disease. Cell Tissue Res. 2010, 339: 167-188. 10.1007/s00441-009-0866-y.
Ram R, Lorente G, Nikolich K, Urfer R, Foehr E, Nagavarapu U: Discoidin domain receptor-1a (DDR1a) promotes glioma cell invasion and adhesion in association with matrix metalloproteinase-2. J Neurooncol. 2006, 76: 239-248. 10.1007/s11060-005-6874-1.
Xue M, Jackson CJ: Autocrine actions of matrix metalloproteinase (MMP)-2 counter the effects of MMP-9 to promote survival and prevent terminal differentiation of cultured human keratinocytes. J Invest Dermatol. 2008, 128: 2676-2685. 10.1038/jid.2008.136.
Nakamura H, Fujii Y, Ohuchi E, Yamamoto E, Okada Y: Activation of the precursor of human stromelysin 2 and its interactions with other matrix metalloproteinases. Eur J Biochem. 1998, 253: 67-75. 10.1046/j.1432-1327.1998.2530067.x.
Krampert M, Bloch W, Sasaki T, Bugnon P, Rulicke T, Wolf E, Aumailley M, Parks WC, Werner S: Activities of the matrix metalloproteinase stromelysin-2 (MMP-10) in matrix degradation and keratinocyte organization in wounded skin. Mol Biol Cell. 2004, 15: 5242-5254. 10.1091/mbc.E04-02-0109.
Gearing AJH, Beckett P, Christodoulou M, Churchill M, Clements J, Davidson AH, Drummond AH, Galloway WA, Gilbert R, Gordon JL, Leber TM, Mangan M, Miller K, Nayee P, Owen K, Patel S, Thomas W, Wells G, Wood LM, Woolley K: Processing of tumour necrosis factor-alpha precursor by metalloproteinases. Nature. 1994, 370: 555-557. 10.1038/370555a0.
Johnson S, Knox A: Autocrine production of matrix metalloproteinase-2 is required for human airway smooth muscle proliferation. Am J Physiol. 1999, 277: L1109-1117.
Xu J, Clark RAF: A three-dimensional collagen lattice induces protein kinase C activity: role in a2 integrin and collagenase mRNA expression. JCB. 1997, 136: 473-483. 10.1083/jcb.136.2.473.
Clark EA, Brugge JS: Integrins and signal transduction pathways: the road taken. Science. 1995, 268: 233-239. 10.1126/science.7716514.
Rowe RG, Weiss SJ: Breaching the basement membrane: who, when and how?. Trends Cell Biol. 2008, 18: 560-574. 10.1016/j.tcb.2008.08.007.
Huang Y, Arora P, McCulloch CA, Vogel WF: The collagen receptor DDR1 regulates cell spreading and motility by associating with myosin IIA. J Cell Sci. 2009, 122: 1637-1646. 10.1242/jcs.046219.