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Respiratory Research
Published in: Respiratory Research 1/2006

Open Access 01-12-2006 | Research

Lung development in laminin γ2 deficiency: abnormal tracheal hemidesmosomes with normal branching morphogenesis and epithelial differentiation

Authors: Nguyet M Nguyen, Leena Pulkkinen, Jessica A Schlueter, Guerrino Meneguzzi, Jouni Uitto, Robert M Senior

Published in: Respiratory Research | Issue 1/2006

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Abstract

Background

Laminin γ2 (Lamc2), one of the polypeptides in laminin-332 (laminin-5), is prominent in the basement membrane of alveolar walls and airways of developing and adult lung. Laminins are important for lung morphogenesis and based on its localization, a function for laminin γ2 in lung development has been hypothesized. Targeted deletion of the laminin γ2 gene in mice results in skin blistering and neonatal death at 3–5 days after birth due to failure to thrive.

Methods

Examination of lung development in Lamc2-/- mice through 1–2 days postnatal was accomplished by morphometric analysis, lung bud culture, electron microscopy, immunohistochemical and immunofluorescence staining.

Results

Compared to littermate controls, Lamc2-/- lungs were similar in morphology during embryonic life. At post-natal day 1–2, distal saccules were mildly dilated by chord length measurements. Epithelial differentiation as evaluated by immunohistochemical staining for markers of ciliated cells, Clara cells, alveolar type I cells and alveolar type II cells did not reveal a difference between Lamc2-/- and littermate control lungs. Likewise, vascular development, smooth muscle cell differentiation, and elastic fiber formation looked similar, as did airway basement membrane ultrastructure. Branching morphogenesis by lung bud culture was similar in Lamc2-/- and littermate control lungs. Since laminin-332 is important for hemidesmosome formation, we examined the structure of tracheal hemidesmosomes by transmission electron microscopy. Compared to littermate controls, Lamc2-/- tracheal hemidesmosomes were less organized and lacked the increased electron density associated with the basement membrane abutting the hemidesmosome.

Conclusion

These findings indicate that laminin γ2 and laminin-332, despite their prominence in the lung, have a minimal role in lung development through the saccular stage.
Literature
1.
Miner JH, Yurchenco PD: Laminin functions in tissue morphogenesis. Annu Rev Cell Dev Biol 2004, 20:255–284.PubMedCrossRef
2.
Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P, Engel J, Engvall E, Hohenester E, Jones JC, Kleinman HK, Marinkovich MP, Martin GR, Mayer U, Meneguzzi G, Miner JH, Miyazaki K, Patarroyo M, Paulsson M, Quaranta V, Sanes JR, Sasaki T, Sekiguchi K, Sorokin LM, Talts JF, Tryggvason K, Uitto J, Virtanen I, von der Mark K, Wewer UM, Yamada Y, Yurchenco PD: A simplified laminin nomenclature. Matrix Biol 2005,24(5):326–332.PubMedCrossRef
3.
Gersdorff N, Kohfeldt E, Sasaki T, Timpl R, Miosge N: Laminin gamma3 chain binds to nidogen and is located in murine basement membranes. J Biol Chem 2005,280(23):22146–22153.PubMedCrossRef
4.
Miner JH, Patton BL, Lentz SI, Gilbert DJ, Snider WD, Jenkins NA, Copeland NG, Sanes JR: The laminin alpha chains: expression, developmental transitions, and chromosomal locations of alpha1–5, identification of heterotrimeric laminins 8–11, and cloning of a novel alpha3 isoform. J Cell Biol 1997,137(3):685–701.PubMedPubMedCentralCrossRef
5.
Virtanen I, Laitinen A, Tani T, Paakko P, Laitinen LA, Burgeson RE, Lehto VP: Differential expression of laminins and their integrin receptors in developing and adult human lung. Am J Respir Cell Mol Biol 1996,15(2):184–196.PubMedCrossRef
6.
Pierce RA, Griffin GL, Mudd MS, Moxley MA, Longmore WJ, Sanes JR, Miner JH, Senior RM: Expression of laminin alpha3, alpha4, and alpha5 chains by alveolar epithelial cells and fibroblasts. Am J Respir Cell Mol Biol 1998,19(2):237–244.PubMedCrossRef
7.
Virtanen I, Gullberg D, Rissanen J, Kivilaakso E, Kiviluoto T, Laitinen LA, Lehto VP, Ekblom P: Laminin alpha1-chain shows a restricted distribution in epithelial basement membranes of fetal and adult human tissues. Exp Cell Res 2000,257(2):298–309.PubMedCrossRef
8.
Schuger L, O'Shea S, Rheinheimer J, Varani J: Laminin in lung development: effects of anti-laminin antibody in murine lung morphogenesis. Dev Biol 1990,137(1):26–32.PubMedCrossRef
9.
Willem M, Miosge N, Halfter W, Smyth N, Jannetti I, Burghart E, Timpl R, Mayer U: Specific ablation of the nidogen-binding site in the laminin gamma1 chain interferes with kidney and lung development. Development 2002,129(11):2711–2722.PubMed
10.
Relan NK, Yang Y, Beqaj S, Miner JH, Schuger L: Cell elongation induces laminin alpha2 chain expression in mouse embryonic mesenchymal cells: role in visceral myogenesis. J Cell Biol 1999,147(6):1341–1350.PubMedPubMedCentralCrossRef
11.
Nguyen NM, Kelley DG, Schlueter JA, Meyer MJ, Senior RM, Miner JH: Epithelial laminin alpha5 is necessary for distal epithelial cell maturation, VEGF production, and alveolization in the developing murine lung. Dev Biol 2005,282(1):111–125.PubMedCrossRef
12.
Mizushima H, Koshikawa N, Moriyama K, Takamura H, Nagashima Y, Hirahara F, Miyazaki K: Wide distribution of laminin-5 gamma 2 chain in basement membranes of various human tissues. Horm Res 1998,50(Suppl 2):7–14.PubMed
13.
Miosge N, Kluge JG, Studzinski A, Zelent C, Bode C, Sprysch P, Burgeson RE, Herken R: In situ-RT-PCR and immunohistochemistry for the localisation of the mRNA of the alpha 3 chain of laminin and laminin-5 during human organogenesis. Anat Embryol (Berl) 2002,205(5–6):355–63. Epub 2002 Jun 28..CrossRef
14.
Coraux C, Meneguzzi G, Rousselle P, Puchelle E, Gaillard D: Distribution of laminin 5, integrin receptors, and branching morphogenesis during human fetal lung development. Dev Dyn 2002,225(2):176–185.PubMedCrossRef
15.
Meng X, Klement JF, Leperi DA, Birk DE, Sasaki T, Timpl R, Uitto J, Pulkkinen L: Targeted inactivation of murine laminin gamma2-chain gene recapitulates human junctional epidermolysis bullosa. J Invest Dermatol 2003,121(4):720–731.PubMedCrossRef
16.
Garbe JH, Gohring W, Mann K, Timpl R, Sasaki T: Complete sequence, recombinant analysis and binding to laminins and sulphated ligands of the N-terminal domains of laminin alpha3B and alpha5 chains. Biochem J 2002,362(Pt 1):213–221.PubMedPubMedCentralCrossRef
17.
Senior RM, Griffin GL, Mudd MS, Moxley MA, Longmore WJ, Pierce RA: Entactin expression by rat lung and rat alveolar epithelial cells. Am J Respir Cell Mol Biol 1996,14(3):239–247.PubMedCrossRef
18.
Nguyen NM, Miner JH, Pierce RA, Senior RM: Laminin alpha 5 is required for lobar septation and visceral pleural basement membrane formation in the developing mouse lung. Dev Biol 2002,246(2):231–244.PubMedCrossRef
19.
Yuen HW, Ziober AF, Gopal P, Nasrallah I, Falls EM, Meneguzzi G, Ang HQ, Ziober BL: Suppression of laminin-5 expression leads to increased motility, tumorigenicity, and invasion. Exp Cell Res 2005,309(1):198–210.PubMedCrossRef
20.
Atkinson JJ, Holmbeck K, Yamada S, Birkedal-Hansen H, Parks WC, Senior RM: Membrane-type 1 matrix metalloproteinase is required for normal alveolar development. Dev Dyn 2005,232(4):1079–1090.PubMedCrossRef
21.
Noakes PG, Miner JH, Gautam M, Cunningham JM, Sanes JR, Merlie JP: The renal glomerulus of mice lacking s-laminin/laminin beta 2: nephrosis despite molecular compensation by laminin beta 1. Nat Genet 1995,10(4):400–406.PubMedCrossRef
22.
Patton BL, Miner JH, Chiu AY, Sanes JR: Distribution and function of laminins in the neuromuscular system of developing, adult, and mutant mice. J Cell Biol 1997,139(6):1507–1521.PubMedPubMedCentralCrossRef
23.
Uitto J, Richard G: Progress in epidermolysis bullosa: genetic classification and clinical implications. Am J Med Genet C Semin Med Genet 2004,131C(1):61–74.PubMedCrossRef
24.
Michelson PH, Tigue M, Jones JC: Human bronchial epithelial cells secrete laminin 5, express hemidesmosomal proteins, and assemble hemidesmosomes. J Histochem Cytochem 2000,48(4):535–544.PubMedCrossRef
25.
Kikkawa Y, Virtanen I, Miner JH: Mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin alpha5 in the glomerular basement membrane. J Cell Biol 2003,161(1):187–96. Epub 2003 Apr 7..PubMedPubMedCentralCrossRef
26.
Verrando P, Hsi BL, Yeh CJ, Pisani A, Serieys N, Ortonne JP: Monoclonal antibody GB3, a new probe for the study of human basement membranes and hemidesmosomes. Exp Cell Res 1987,170(1):116–128.PubMedCrossRef
27.
Carter WG, Ryan MC, Gahr PJ: Epiligrin, a new cell adhesion ligand for integrin alpha 3 beta 1 in epithelial basement membranes. Cell 1991,65(4):599–610.PubMedCrossRef
28.
Aberdam D, Aguzzi A, Baudoin C, Galliano MF, Ortonne JP, Meneguzzi G: Developmental expression of nicein adhesion protein (laminin-5) subunits suggests multiple morphogenic roles. Cell Adhes Commun 1994,2(2):115–129.PubMedCrossRef
29.
Ryan MC, Lee K, Miyashita Y, Carter WG: Targeted disruption of the LAMA3 gene in mice reveals abnormalities in survival and late stage differentiation of epithelial cells. J Cell Biol 1999,145(6):1309–1323.PubMedPubMedCentralCrossRef
30.
Kuster JE, Guarnieri MH, Ault JG, Flaherty L, Swiatek PJ: IAP insertion in the murine LamB3 gene results in junctional epidermolysis bullosa. Mamm Genome 1997,8(9):673–681.PubMedCrossRef
31.
Kreidberg JA, Donovan MJ, Goldstein SL, Rennke H, Shepherd K, Jones RC, Jaenisch R: Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis. Development 1996,122(11):3537–3547.PubMed
32.
Olsen CO, Isakson BE, Seedorf GJ, Lubman RL, Boitano S: Extracellular matrix-driven alveolar epithelial cell differentiation in vitro. Exp Lung Res 2005,31(5):461–482.PubMedCrossRef
33.
Isakson BE, Lubman RL, Seedorf GJ, Boitano S: Modulation of pulmonary alveolar type II cell phenotype and communication by extracellular matrix and KGF. Am J Physiol Cell Physiol 2001,281(4):C1291–9.PubMed
34.
Isakson BE, Seedorf GJ, Lubman RL, Boitano S: Heterocellular cultures of pulmonary alveolar epithelial cells grown on laminin-5 supplemented matrix. In Vitro Cell Dev Biol Anim 2002,38(8):443–449.PubMedCrossRef
35.
Miner JH, Cunningham J, Sanes JR: Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain. J Cell Biol 1998,143(6):1713–1723.PubMedPubMedCentralCrossRef
36.
Bolcato-Bellemin AL, Lefebvre O, Arnold C, Sorokin L, Miner JH, Kedinger M, Simon-Assmann P: Laminin alpha5 chain is required for intestinal smooth muscle development. Dev Biol 2003,260(2):376–390.PubMedCrossRef
37.
Smith LT, Miller AW, Kirz DA, Elias S, Brumbaugh S, Holbrook KA: Separation of noncutaneous epithelia in a fetus diagnosed in utero with junctional epidermolysis bullosa. Pediatr Res 1992,31(6):561–566.PubMedCrossRef
38.
Thompson JW, Ahmed AR, Dudley JP: Epidermolysis bullosa dystrophica of the larynx and trachea. Acute airway obstruction. Ann Otol Rhinol Laryngol 1980,89(5 Pt 1):428–429.PubMedCrossRef
39.
Liu RM, Papsin BC, de Jong AL: Epidermolysis bullosa of the head and neck: a case report of laryngotracheal involvement and 10-year review of cases at the Hospital for Sick Children. J Otolaryngol 1999,28(2):76–82.PubMed
40.
Lappi-Blanco E, Kaarteenaho-Wiik R, Salo S, Sormunen R, Maatta M, Autio-Harmainen H, Soini Y, Paakko P: Laminin-5 gamma2 chain in cryptogenic organizing pneumonia and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2004,169(1):27–33. Epub 2003 Sep 18..PubMedCrossRef
41.
Amin K, Janson C, Seveus L, Miyazaki K, Virtanen I, Venge P: Uncoordinated production of Laminin-5 chains in airways epithelium of allergic asthmatics. Respir Res 2005, 6:110.PubMedPubMedCentralCrossRef
42.
Katayama M, Sekiguchi K: Laminin-5 in epithelial tumour invasion. J Mol Histol 2004,35(3):277–286.PubMedCrossRef
43.
Mizushima H, Miyagi Y, Kikkawa Y, Yamanaka N, Yasumitsu H, Misugi K, Miyazaki K: Differential expression of laminin-5/ladsin subunits in human tissues and cancer cell lines and their induction by tumor promoter and growth factors. J Biochem (Tokyo) 1996,120(6):1196–1202.CrossRef
44.
Maatta M, Soini Y, Paakko P, Salo S, Tryggvason K, Autio-Harmainen H: Expression of the laminin gamma2 chain in different histological types of lung carcinoma. A study by immunohistochemistry and in situ hybridization. J Pathol 1999,188(4):361–368.PubMedCrossRef
45.
Sathyanarayana UG, Toyooka S, Padar A, Takahashi T, Brambilla E, Minna JD, Gazdar AF: Epigenetic inactivation of laminin-5-encoding genes in lung cancers. Clin Cancer Res 2003,9(7):2665–2672.PubMed
46.
Sathyanarayana UG, Padar A, Suzuki M, Maruyama R, Shigematsu H, Hsieh JT, Frenkel EP, Gazdar AF: Aberrant promoter methylation of laminin-5-encoding genes in prostate cancers and its relationship to clinicopathological features. Clin Cancer Res 2003,9(17):6395–6400.PubMed
47.
Sathyanarayana UG, Maruyama R, Padar A, Suzuki M, Bondaruk J, Sagalowsky A, Minna JD, Frenkel EP, Grossman HB, Czerniak B, Gazdar AF: Molecular detection of noninvasive and invasive bladder tumor tissues and exfoliated cells by aberrant promoter methylation of laminin-5 encoding genes. Cancer Res 2004,64(4):1425–1430.PubMedCrossRef
48.
Kagesato Y, Mizushima H, Koshikawa N, Kitamura H, Hayashi H, Ogawa N, Tsukuda M, Miyazaki K: Sole expression of laminin gamma 2 chain in invading tumor cells and its association with stromal fibrosis in lung adenocarcinomas. Jpn J Cancer Res 2001,92(2):184–192.PubMedCrossRef
Metadata
Title
Lung development in laminin γ2 deficiency: abnormal tracheal hemidesmosomes with normal branching morphogenesis and epithelial differentiation
Authors
Nguyet M Nguyen
Leena Pulkkinen
Jessica A Schlueter
Guerrino Meneguzzi
Jouni Uitto
Robert M Senior
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2006
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-7-28

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