272
Views
27
CrossRef citations to date
0
Altmetric
Review

Lung epithelial wound healing in health and disease

, &
Pages 647-660 | Published online: 09 Jan 2014

References

  • van Wetering S, Sterk PJ, Rabe KF, Hiemstra PS. Defensins: key players or bystanders in infection, injury, and repair in the lung? J. Allergy Clin. Immunol.104(6), 1131–1138 (1999).
  • Hiemstra PS. The role of epithelial β-defensins and cathelicidins in host defense of the lung. Exp. Lung Res.33(10), 537–542 (2007).
  • Sallenave J. Secretory leukocyte protease inhibitor and elafin/trappin-2: versatile mucosal antimicrobials and regulators of immunity. Am. J. Respir. Cell Mol. Biol.42(6), 635–643 (2010).
  • Tang L, Wu JJ, Ma Q et al. Human lactoferrin stimulates skin keratinocyte function and wound reepithelialization. Br. J. Dermatol.163(1), 38–47 (2010).
  • Persson CG, Erjefält JS, Greiff L et al. Plasma-derived proteins in airway defence, disease and repair of epithelial injury. Eur. Respir. J.11(4), 958–970 (1998).
  • Galiacy S, Planus E, Lepetit H et al. Keratinocyte growth factor promotes cell motility during alveolar epithelial repair in vitro. Exp. Cell Res.283(2), 215–229 (2003).
  • Kim SH, Matthay MA, Mostov K, Hunt CA. Simulation of lung alveolar epithelial wound healing in vitro. J. R. Soc. Interface7(49), 1157–1170 (2010).
  • Lucas R, Verin AD, Black SM, Catravas JD. Regulators of endothelial and epithelial barrier integrity and function in acute lung injury. Biochem. Pharmacol.77(12), 1763–1772 (2009).
  • Holgate ST. The airway epithelium is central to the pathogenesis of asthma. Allergol. Int.57(1), 1–10 (2008).
  • Behzad AR, McDonough JE, Seyednejad N, Hogg JC, Walker DC. The disruption of the epithelial mesenchymal trophic unit in COPD. COPD6(6), 421–431 (2009).
  • Stoscheck CM, Nanney LB, King LE. Quantitative determination of EGF-R during epidermal wound healing. J. Invest. Dermatol.99(5), 645–649 (1992).
  • Xu YD, Hua J, Mui A et al. Release of biologically active TGF-β1 by alveolar epithelial cells results in pulmonary fibrosis. Am. J. Physiol. Lung Cell Mol. Physiol.285(3), 527–539 (2003).
  • Oikonomou N, Harokopos V, Zalevsky J et al. Soluble TNF mediates the transition from pulmonary inflammation to fibrosis. PloS ONE1, e108 (2006).
  • Kolb M, Margetts PJ, Anthony DC, Pitossi F, Gauldie J. Transient expression of IL-1β induces acute lung injury and chronic repair leading to pulmonary fibrosis. J. Clin. Invest.107(12), 1529–1536 (2001).
  • Crosby LM, Waters CM. Epithelial repair mechanisms in the lung. Am. J. Physiol. Lung Cell Mol. Physiol.298, 715–731 (2010).
  • Bartram U, Speer CP. The role of transforming growth factor β in lung development and disease. Chest125(2), 754–765 (2004).
  • Hackett T, Warner SM, Stefanowicz D et al. Induction of epithelial-mesenchymal transition in primary airway epithelial cells from patients with asthma by transforming growth factor-β1. Am. J. Respir. Crit. Care Med.180(2), 122–133 (2009).
  • Borthwick L, Parker S, Brougham K et al. Epithelial to mesenchymal transition (EMT) and airway remodelling after human lung transplantation. Thorax64(9), 770–777 (2009).
  • Morty RE, Königshoff M, Eickelberg O. Transforming growth factor-β signaling across ages: from distorted lung development to chronic obstructive pulmonary disease. Proc. Am. Thorac. Soc.6(7), 607–613 (2009).
  • Moustakas A, Heldin C. The regulation of TGFβ signal transduction. Development136(22), 3699–3714 (2009).
  • Gill SE, Parks WC. Metalloproteinases and their inhibitors: regulators of wound healing. Int. J. Biochem. Cell Biol.40(6–7), 1334–1347 (2008).
  • Li Q, Park PW, Wilson CL, Parks WC. Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell111(5), 635–646 (2002).
  • Brew K, Nagase H. The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim. Biophys. Acta1803(1), 55–71 (2010).
  • Murphy G, Nagase H. Progress in matrix metalloproteinase research. Mol. Aspects Med.29(5), 290–308 (2008).
  • Clark RAF. The Molecular And Cellular Biology Of Wound Repair. Springer, NY, USA (1996).
  • Santos FB, Nagato LK, Boechem NM et al. Time course of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury. J. Appl. Physiol.100(1), 98–106 (2006).
  • Junqueira LC, Montes GS. Biology of collagen–proteoglycan interaction. Arch. Histol. Jpn46(5), 589–629 (1983).
  • Ehrlich HP. Wound closure: evidence of cooperation between fibroblasts and collagen matrix. Eye (Lond).2(Pt 2), 149–157 (1988).
  • Behr J, Kolb M, Cox G. Treating IPF – all or nothing? A PRO-CON debate. Respirology14(8), 1072–1081 (2009).
  • Harari S, Caminati A. IPF: new insight on pathogenesis and treatment. Allergy65(5), 537–553 (2010).
  • Sime PJ, Xing Z, Graham FL, Csaky KG, Gauldie J. Adenovector-mediated gene transfer of active transforming growth factor-β1 induces prolonged severe fibrosis in rat lung. J. Clin. Invest.100(4), 768–776 (1997).
  • Gauldie J, Bonniaud P, Sime P, Ask K, Kolb M. TGF-β, Smad3 and the process of progressive fibrosis. Biochem. Soc. Trans.35(Pt 4), 661–664 (2007).
  • Hiwatari N, Shimura S, Yamauchi K et al. Significance of elevated procollagen-III-peptide and transforming growth factor-β levels of bronchoalveolar lavage fluids from idiopathic pulmonary fibrosis patients. Tohoku J. Exp. Med.181(2), 285–295 (1997).
  • Borthwick LA, McIlroy EI, Gorowiec MR et al. Inflammation and epithelial to mesenchymal transition in lung transplant recipients: role in dysregulated epithelial wound repair. Am. J. Transplant.10(3), 498–509 (2010).
  • Borthwick LA, Parker SM, Brougham KA et al. Epithelial to mesenchymal transition (EMT) and airway remodelling after human lung transplantation. Thorax64(9), 770–777 (2009).
  • Frolik CA, Wakefield LM, Smith DM, Sporn MB. Characterization of a membrane receptor for transforming growth factor-β in normal rat kidney fibroblasts. J. Biol. Chem.259(17), 10995–11000 (1984).
  • Savill J. Phagocyte recognition of apoptotic cells. Biochem. Soc. Trans.24(4), 1065–1069 (1996).
  • Wahl SM, Hunt DA, Wakefield LM et al. Transforming growth factor type β induces monocyte chemotaxis and growth factor production. Proc. Natl Acad. Sci. USA84(16), 5788–5792 (1987).
  • Monteseirín J. Neutrophils and asthma. J. Investig. Allergol. Clin. Immunol.19(5), 340–354 (2009).
  • Turlej RK, Fiévez L, Sandersen CF et al. Enhanced survival of lung granulocytes in an animal model of asthma: evidence for a role of GM-CSF activated STAT5 signalling pathway. Thorax56(9), 696–702 (2001).
  • Cosgrove GP, Schwarz MI, Geraci MW, Brown KK, Worthen GS. Overexpression of matrix metalloproteinase-7 in pulmonary fibrosis. Chest121(3), 255–265 (2002).
  • Zoutman DE, Hulbert WC, Pasloske BL et al. The role of polar pili in the adherence of Pseudomonas aeruginosa to injured canine tracheal cells: a semiquantitative morphologic study. Scanning Microsc.5(1), 109–124; discussion 124–126 (1991).
  • Plotkowski MC, Chevillard M, Pierrot D et al. Differential adhesion of Pseudomonas aeruginosa to human respiratory epithelial cells in primary culture. J. Clin. Invest.87(6), 2018–2028 (1991).
  • King P, Holdsworth S, Freezer N, Holmes P. Bronchiectasis. Intern. Med. J.36(11), 729–737 (2006).
  • Hetzel M, Bachem M, Anders D, Trischler G, Faehling M. Different effects of growth factors on proliferation and matrix production of normal and fibrotic human lung fibroblasts. Lung183(4), 225–237 (2005).
  • Gordon S. Alternative activation of macrophages. Nat. Rev. Immunol.3(1), 23–35 (2003).
  • Aron-Wisnewsky J, Tordjman J, Poitou C et al. Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J. Clin. Endocrinol. Metab.94(11), 4619–4623 (2009).
  • Kristiansen M, Graversen JH, Jacobsen C et al. Identification of the haemoglobin scavenger receptor. Nature409(6817), 198–201 (2001).
  • Goerdt S, Orfanos CE. Other functions, other genes: alternative activation of antigen-presenting cells. Immunity10(2), 137–142 (1999).
  • Porcheray F, Viaud S, Rimaniol A et al. Macrophage activation switching: an asset for the resolution of inflammation. Clin. Exp. Immunol.142(3), 481–489 (2005).
  • Martin P, D’Souza D, Martin J et al. Wound healing in the PU.1 null mouse –tissue repair is not dependent on inflammatory cells. Curr. Biol.13(13), 1122–1128 (2003).
  • Bellingan GJ, Caldwell H, Howie SE, Dransfield I, Haslett C. in vivo fate of the inflammatory macrophage during the resolution of inflammation: inflammatory macrophages do not die locally, but emigrate to the draining lymph nodes. J. Immunol.157(6), 2577–2585 (1996).
  • Hsu L, Park JM, Zhang K et al. The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature428(6980), 341–345 (2004).
  • Gharaee-Kermani M, Hu B, Thannickal VJ, Phan SH, Gyetko MR. Current and emerging drugs for idiopathic pulmonary fibrosis. Expert Opin. Emerg. Drugs12(4), 627–646 (2007).
  • Sharma S, Ghosh B, Sharma SK. Association of TNF polymorphisms with sarcoidosis, its prognosis and tumour necrosis factor (TNF)-α levels in Asian Indians. Clin. Exp. Immunol.151(2), 251–259 (2008).
  • Riha RL, Yang IA, Rabnott GC et al. Cytokine gene polymorphisms in idiopathic pulmonary fibrosis. Intern. Med. J.34(3), 126–129 (2004).
  • Krein PM, Yong H, Winston BW. Growth factor regulation and manipulation in wound repair: to scar or not to scar, that is the question. Expert Opin. Ther. Pat.11(7), 1065–1079 (2001).
  • Lasky JA, Brody AR. Interstitial fibrosis and growth factors. Environ. Health Perspect.108(Suppl.), 751–762 (2000).
  • Krein PM, Winston BW. Roles for insulin-like growth factor I and transforming growth factor-β in fibrotic lung disease. Chest122(6 Suppl.), 289S–293S (2002).
  • Hinz B, Celetta G, Tomasek JJ, Gabbiani G, Chaponnier C. α-smooth muscle actin expression upregulates fibroblast contractile activity. Mol. Biol. Cell12(9), 2730–2741 (2001).
  • Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A. Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol. Med.1(1), 71–81 (1994).
  • Quan TE, Cowper S, Wu S, Bockenstedt LK, Bucala R. Circulating fibrocytes: collagen-secreting cells of the peripheral blood. Int. J. Biochem. Cell Biol.36(4), 598–606 (2004).
  • Abe R, Donnelly SC, Peng T, Bucala R, Metz CN. Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J. Immunol.166(12), 7556–7562 (2001).
  • Moeller A, Gilpin SE, Ask K et al. Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med.179(7), 588–594 (2009).
  • Saunders R, Siddiqui S, Kaur D et al. Fibrocyte localization to the airway smooth muscle is a feature of asthma. J. Allergy Clin. Immunol.123(2), 376–384 (2009).
  • Sacco O, Silvestri M, Sabatini F et al. Epithelial cells and fibroblasts: structural repair and remodelling in the airways. Paediatr. Respir. Rev.5, S35–S40 (2004).
  • Harris AK, Stopak D, Wild P. Fibroblast traction as a mechanism for collagen morphogenesis. Nature290(5803), 249–251 (1981).
  • Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat. Rev. Mol. Cell Biol.3(5), 349–363 (2002).
  • Kuhn C, Boldt J, King TE et al. An immunohistochemical study of architectural remodeling and connective tissue synthesis in pulmonary fibrosis. Am. Rev. Respir. Dis.140(6), 1693–1703 (1989).
  • Hinz B. Formation and function of the myofibroblast during tissue repair. J. Invest. Dermatol.127(3), 526–537 (2007).
  • Bogatkevich GS, Tourkina E, Silver RM, Ludwicka-Bradley A. Thrombin differentiates normal lung fibroblasts to a myofibroblast phenotype via the proteolytically activated receptor-1 and a protein kinase C-dependent pathway. J. Biol. Chem.276(48), 45184–45192 (2001).
  • Eddy RJ, Petro JA, Tomasek JJ. Evidence for the nonmuscle nature of the ‘myofibroblast’ of granulation tissue and hypertropic scar. An immunofluorescence study. Am. J. Pathol.130(2), 252–260 (1988).
  • Darby I, Skalli O, Gabbiani G. a-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab. Invest.63(1), 21–29 (1990).
  • Dugina V, Fontao L, Chaponnier C, Vasiliev J, Gabbiani G. Focal adhesion features during myofibroblastic differentiation are controlled by intracellular and extracellular factors. J. Cell. Sci.114(Pt 18), 3285–3296 (2001).
  • Gabbiani G, Chaponnier C, Hüttner I. Cytoplasmic filaments and gap junctions in epithelial cells and myofibroblasts during wound healing. J. Cell Biol.76(3), 561–568 (1978).
  • Bullard KM, Lund L, Mudgett JS et al. Impaired wound contraction in stromelysin-1-deficient mice. Ann. Surg.230(2), 260–265 (1999).
  • Hinz B, Gabbiani G. Mechanisms of force generation and transmission by myofibroblasts. Curr. Opin. Biotechnol.14(5), 538–546 (2003).
  • Desmoulière A, Redard M, Darby I, Gabbiani G. Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am. J. Pathol.146(1), 56–66 (1995).
  • Carlson MA, Longaker MT, Thompson JS. Wound splinting regulates granulation tissue survival. J. Surg. Res.110(1), 304–309 (2003).
  • Jamora C, Fuchs E. Intercellular adhesion, signalling and the cytoskeleton. Nat. Cell Biol.4(4), E101–E108 (2002).
  • Petridou S, Maltseva O, Spanakis S, Masur SK. TGF-β receptor expression and smad2 localization are cell density dependent in fibroblasts. Invest. Ophthalmol. Vis. Sci.41(1), 89–95 (2000).
  • Cool CD, Groshong SD, Rai PR et al. Fibroblast foci are not discrete sites of lung injury or repair: the fibroblast reticulum. Am. J. Respir. Crit. Care Med.174(6), 654–658 (2006).
  • Zegers MM, Forget M, Chernoff J et al. Pak1 and PIX regulate contact inhibition during epithelial wound healing. EMBO J.22(16), 4155–4165 (2003).
  • Nelson WJ. Remodeling epithelial cell organization: transitions between front-rear and apical-basal polarity. Cold Spring Harb. Perspect. Biol.1(1), a000513 (2009).
  • Werner S. Keratinocyte growth factor: a unique player in epithelial repair processes. Cytokine Growth Factor Rev.9(2), 153–165 (1998).
  • Bianco A, Poukkula M, Cliffe A et al. Two distinct modes of guidance signalling during collective migration of border cells. Nature448(7151), 362–365 (2007).
  • Itoh RE, Kurokawa K, Ohba Y et al. Activation of Rac and Cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells. Mol. Cell. Biol.22(18), 6582–6591 (2002).
  • Farooqui R, Fenteany G. Multiple rows of cells behind an epithelial wound edge extend cryptic lamellipodia to collectively drive cell-sheet movement. J. Cell. Sci.118(Pt 1), 51–63 (2005).
  • DiMilla PA, Stone JA, Quinn JA, Albelda SM, Lauffenburger DA. Maximal migration of human smooth muscle cells on fibronectin and type IV collagen occurs at an intermediate attachment strength. J. Cell Biol.122(3), 729–737 (1993).
  • Lawson MA, Maxfield FR. Ca2+- and calcineurin-dependent recycling of an integrin to the front of migrating neutrophils. Nature377(6544), 75–79 (1995).
  • Mattila PK, Lappalainen P. Filopodia: molecular architecture and cellular functions. Nat. Rev. Mol. Cell Biol.9(6), 446–454 (2008).
  • Condeelis J. Life at the leading edge: the formation of cell protrusions. Annu. Rev. Cell Biol.9, 411–444 (1993).
  • Nobes CD. Rho GTPases control polarity, protrusion, and adhesion during cell movement. J. Cell Biol.144(6), 1235–1244 (1999).
  • Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell70(3), 401–410 (1992).
  • Pilewski JM, Latoche JD, Arcasoy SM, Albelda SM. Expression of integrin cell adhesion receptors during human airway epithelial repair in vivo. Am. J. Physiol.273(1 Pt 1), L256–L263 (1997).
  • Vaughan RB, Trinkaus JP. Movements of epithelial cell sheets in vitro. J. Cell. Sci.1(4), 407–413 (1966).
  • Munger JS, Huang X, Kawakatsu H et al. The integrin α v β 6 binds and activates latent TGF β 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell96(3), 319–328 (1999).
  • Mu D, Cambier S, Fjellbirkeland L et al. The integrin α(v)β8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-β1. J. Cell Biol.157(3), 493–507 (2002).
  • Massagué J, Chen YG. Controlling TGF-β signaling. Genes Dev.14(6), 627–644 (2000).
  • Pechkovsky DV, Scaffidi AK, Hackett TL et al. Transforming growth factor β1 induces αvβ3 integrin expression in human lung fibroblasts via a β3 integrin-, c-Src-, and p38 MAPK-dependent pathway. J. Biol. Chem.283(19), 12898–12908 (2008).
  • Kim KK, Wei Y, Szekeres C et al. Epithelial cell α3β1 integrin links β-catenin and Smadsignaling to promote myofibroblast formation and pulmonary fibrosis. J. Clin. Invest.119(1), 213–224 (2009).
  • Thompson EE, Pan L, Ostrovnaya I et al. Integrin β 3 genotype influences asthma and allergy phenotypes in the first 6 years of life. J. Allergy Clin. Immunol.119(6), 1423–1429 (2007).
  • Rogers AJ, Raby BA, Lasky-Su JA et al. Assessing the reproducibility of asthma candidate gene associations, using genome-wide data. Am. J. Respir. Crit. Care Med.179(12), 1084–1090 (2009).
  • Reynolds LE, Conti FJ, Lucas M et al. Accelerated re-epithelialization in β3-integrin-deficient- mice is associated with enhanced TGF-β1 signaling. Nat. Med.11(2), 167–174 (2005).
  • Pauwels R, Pedersen S, Busse W et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet361(9363), 1071–1076 (2003).
  • Mautino G, Oliver N, Chanez P, Bousquet J, Capony F. Increased release of matrix metalloproteinase-9 in bronchoalveolar lavage fluid and by alveolar macrophages of asthmatics. Am. J. Respir. Cell Mol. Biol.17(5), 583–591 (1997).
  • Cataldo DD, Gueders M, Munaut C et al. Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases mRNA transcripts in the bronchial secretions of asthmatics. Lab. Invest.84(4), 418–424 (2004).
  • Ohno I, Ohtani H, Nitta Y et al. Eosinophils as a source of matrix metalloproteinase-9 in asthmatic airway inflammation. Am. J. Respir. Cell Mol. Biol.16(3), 212–219 (1997).
  • Cho JY, Miller M, McElwain K et al. Remodeling associated expression of matrix metalloproteinase 9 but not tissue inhibitor of metalloproteinase 1 in airway epithelium: modulation by immunostimulatory DNA. J. Allergy Clin. Immunol.117(3), 618–625 (2006).
  • Han Z. Expression of matrix metalloproteinases MMP-9 within the airways in asthma. Respir. Med.97(5), 563–567 (2003).
  • Matsumoto H, Niimi A, Takemura M et al. Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthma. Thorax60(4), 277–281 (2005).
  • Cataldo DD, Bettiol J, Noël A et al. Matrix metalloproteinase-9, but not tissue inhibitor of matrix metalloproteinase-1, increases in the sputum from allergic asthmatic patients after allergen challenge. Chest122(5), 1553–1559 (2002).
  • McGuire JK, Li Q, Parks WC. Matrilysin (matrix metalloproteinase-7) mediates E-cadherin ectodomain shedding in injured lung epithelium. Am. J. Pathol.162(6), 1831–1843 (2003).
  • Dunsmore SE, Saarialho-Kere UK, Roby JD et al. Matrilysin expression and function in airway epithelium. J. Clin. Invest.102(7), 1321–1331 (1998).
  • Roeb E, Winograd R, Breuer B, Nguyen H, Matern S. Increased TIMP-1 activity results in increased expression of gelatinases and altered cell motility. J. Cell. Biochem.75(2), 346–355 (1999).
  • Chen P, McGuire JK, Hackman RC et al. Tissue inhibitor of metalloproteinase-1 moderates airway re-epithelialization by regulating matrilysin activity. Am. J. Pathol.172(5), 1256–1270 (2008).
  • Chen P, Farivar AS, Mulligan MS, Madtes DK. Tissue inhibitor of metalloproteinase-1 deficiency abrogates obliterative airway disease after heterotopic tracheal transplantation. Am. J. Respir. Cell Mol. Biol.34(4), 464–472 (2006).
  • Mirastschijski U, Haaksma CJ, Tomasek JJ, Agren MS. Matrix metalloproteinase inhibitor GM 6001 attenuates keratinocyte migration, contraction and myofibroblast formation in skin wounds. Exp. Cell Res.299(2), 465–475 (2004).
  • Salonurmi T, Parikka M, Kontusaari S et al. Overexpression of TIMP-1 under the MMP-9 promoter interferes with wound healing in transgenic mice. Cell Tissue Res.315(1), 27–37 (2004).
  • Vasil’ev IM, Gel’fand IM, Domnina LV, Zakharov OS, Liubimov AV. [Influence of intercellular contacts in epithelial sheets on the capacity of the cell surface for adhesion and phagocytosis of particles]. Tsitologiia17(12), 1400–1405 (1975).
  • Desai LP, Chapman KE, Waters CM. Mechanical stretch decreases migration of alveolar epithelial cells through mechanisms involving Rac1 and Tiam1. Am. J. Physiol. Lung Cell Mol. Physiol.295(5), L958–L965 (2008).
  • de Bentzmann S, Roger P, Dupuit F et al. Asialo GM1 is a receptor for Pseudomonas aeruginosa adherence to regenerating respiratory epithelial cells. Infect. Immun.64(5), 1582–1588 (1996).
  • Rock JR, Onaitis MW, Rawlins EL et al. Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc. Natl Acad. Sci. USA106(31), 12771–12775 (2009).
  • Evans MJ, Johnson LV, Stephens RJ, Freeman G. Renewal of the terminal bronchiolar epithelium in the rat following exposure to NO2 or O3. Lab. Invest.35(3), 246–257 (1976).
  • Stripp BR, Reynolds SD. Maintenance and repair of the bronchiolar epithelium. Proc. Am. Thorac. Soc.5(3), 328–333 (2008).
  • Lee Y, Zhang Z, Mukherjee AB. Mice lacking uteroglobin are highly susceptible to developing pulmonary fibrosis. FEBS Lett.580(18), 4515–4520 (2006).
  • Fehrenbach H, Kasper M, Tschernig T et al. Keratinocyte growth factor-induced hyperplasia of rat alveolar type II cells in vivo is resolved by differentiation into type I cells and by apoptosis. Eur. Respir. J.14(3), 534–544 (1999).
  • Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell139(5), 871–890 (2009).
  • Willis BC, Borok Z. TGF-β-induced EMT: mechanisms and implications for fibrotic lung disease. Am. J. Physiol. Lung Cell Mol. Physiol.293(3), L525–L534 (2007).
  • Kim KK, Kugler MC, Wolters PJ et al. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. PNAS103(35), 13180–13185 (2006).
  • Slavkin HC, Cummings E, Bringas P, Honig LS. Epithelial-derived basal lamina regulation of mesenchymal cell differentiation. Prog. Clin. Biol. Res.85(Pt B), 249–259 (1982).
  • Laurie GW, Leblond CP, Martin GR. Localization of type IV collagen, laminin, heparansulfateproteoglycan, and fibronectin to the basal lamina of basement membranes. J. Cell Biol.95(1), 340–344 (1982).
  • Gabbiani G. The myofibroblast in wound healing and fibrocontractive diseases. J. Pathol.200(4), 500–503 (2003).
  • Gueders MM, Foidart J, Noel A, Cataldo DD. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: potential implications in asthma and other lung diseases. Eur. J. Pharmacol.533(1–3), 133–144 (2006).
  • Ehrlich HP, Krummel TM. Regulation of wound healing from a connective tissue perspective. Wound Repair Regen.4(2), 203–210 (1996).
  • Messmer T, Armour R, Holley R. Factors influencing the growth of alveolar type II epithelial cells isolated from rat lungs. Exp. Cell Res.142(2), 417–426 (1982).
  • Charpidou A, Blatza D, Anagnostou V, Anagnostou E, Syrigos KN. Review. EGFR mutations in non-small cell lung cancer – clinical implications. in vivo22(4), 529–536 (2008).
  • Antoniou KM, Soufla G, Lymbouridou R et al. Expression analysis of angiogenic growth factors and biological axis CXCL12/CXCR4 axis in idiopathic pulmonary fibrosis. Connect. Tissue Res.51(1), 71–80 (2010).
  • Jin N, Cho S, Raso MG et al. Mig-6 is required for appropriate lung development and to ensure normal adult lung homeostasis. Development136(19), 3347–3356 (2009).
  • Gottardi CJ, Arpin M, Fanning AS, Louvard D. The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts. Proc. Natl Acad. Sci. USA93(20), 10779–10784 (1996).
  • Curtis CG, Bilyard K, Stephenson H. Ex vivo metrics, a preclinical tool in new drug development. J. Transl. Med.6(1), 5 (2008).
  • Ceresa CC, Knox AJ, Johnson SR. Use of a three-dimensional cell culture model to study airway smooth muscle-mast cell interactions in airway remodeling. Am. J. Physiol. Lung Cell Mol. Physiol.296(6), L1059–L1066 (2009).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.