The Journal of Cell Biology, Vol 109, 903-914, Copyright © 1989 by The Rockefeller University Press

ARTICLES

Reappearance of an embryonic pattern of fibronectin splicing during wound healing in the adult rat

C Ffrench-Constant, L Van de Water, HF Dvorak and RO Hynes
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, 02139.

The adhesive extracellular matrix glycoprotein fibronectin (FN) is thought to play an important role in the cell migration associated with wound healing. Immunolocalization studies show abundant FN in healing wounds; however, these studies cannot define the cellular site(s) of FN synthesis, nor do they distinguish the different and potentially functionally distinct forms of FN that can arise from alternative splicing of the primary gene transcript. To examine these questions of FN synthesis and splicing during wound healing, we have performed in situ hybridization with segment-specific probes on healing wounds in adult rat skin. We find that the FN gene is expressed at increased levels after wounding both in the cells at the base of the wound and in subjacent muscle and dermis lateral to the wound. Interestingly, however, the pattern of splicing of FN mRNA was different in these areas. In adjacent dermis and muscle, the splicing pattern remains identical with that seen in normal adult rat skin, with two of the three spliced segments (EIIIA and EIIIB) excluded from FN mRNA. In contrast, these two segments are included in the FN mRNA present in the cells at the base of the wound. As a result, the mRNA in this region is spliced in a pattern identical with that found during early embryogenesis. The finding that the pattern of FN splicing during wound healing resembles an embryonic pattern suggests that alternative splicing may be used during wound healing as a mechanism to generate forms of FN that may be functionally more appropriate for the cell migration and proliferation associated with tissue repair.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Huang, G., Zhang, Y., Kim, B., Ge, G., Annis, D. S., Mosher, D. F., Greenspan, D. S. (2009). Fibronectin Binds and Enhances the Activity of Bone Morphogenetic Protein 1. J. Biol. Chem. 284: 25879-25888 [Abstract] [Full Text]  
• Sauer, S., Erba, P. A., Petrini, M., Menrad, A., Giovannoni, L., Grana, C., Hirsch, B., Zardi, L., Paganelli, G., Mariani, G., Neri, D., Durkop, H., Menssen, H. D. (2009). Expression of the oncofetal ED-B-containing fibronectin isoform in hematologic tumors enables ED-B-targeted 131I-L19SIP radioimmunotherapy in Hodgkin lymphoma patients. Blood 113: 2265-2274 [Abstract] [Full Text]  
• Muro, A. F., Moretti, F. A., Moore, B. B., Yan, M., Atrasz, R. G., Wilke, C. A., Flaherty, K. R., Martinez, F. J., Tsui, J. L., Sheppard, D., Baralle, F. E., Toews, G. B., White, E. S. (2008). An Essential Role for Fibronectin Extra Type III Domain A in Pulmonary Fibrosis. Am. J. Respir. Crit. Care Med. 177: 638-645 [Abstract] [Full Text]  
• Shinde, A. V., Bystroff, C., Wang, C., Vogelezang, M. G., Vincent, P. A., Hynes, R. O., Van De Water, L. (2008). Identification of the Peptide Sequences within the EIIIA (EDA) Segment of Fibronectin That Mediate Integrin {alpha}9{beta}1-dependent Cellular Activities. J. Biol. Chem. 283: 2858-2870 [Abstract] [Full Text]  
• Li-Korotky, H.-S., Hebda, P. A., Lo, C.-Y., Dohar, J. E. (2007). Age-Dependent Differential Expression of Fibronectin Variants in Skin and Airway Mucosal Wounds. Arch Otolaryngol Head Neck Surg 133: 919-924 [Abstract] [Full Text]  
• Chang, M.-L., Chen, J.-C., Alonso, C. R., Kornblihtt, A. R., Bissell, D. M. (2004). Regulation of fibronectin splicing in sinusoidal endothelial cells from normal or injured liver. Proc. Natl. Acad. Sci. USA 101: 18093-18098 [Abstract] [Full Text]  
• Tan, M. H., Sun, Z., Opitz, S. L., Schmidt, T. E., Peters, J. H., George, E. L. (2004). Deletion of the alternatively spliced fibronectin EIIIA domain in mice reduces atherosclerosis. Blood 104: 11-18 [Abstract] [Full Text]  
• Borsi, L., Balza, E., Carnemolla, B., Sassi, F., Castellani, P., Berndt, A., Kosmehl, H., Biro, A., Siri, A., Orecchia, P., Grassi, J., Neri, D., Zardi, L. (2003). Selective targeted delivery of TNF{alpha} to tumor blood vessels. Blood 102: 4384-4392 [Abstract] [Full Text]  
• Muro, A. F., Chauhan, A. K., Gajovic, S., Iaconcig, A., Porro, F., Stanta, G., Baralle, F. E. (2003). Regulated splicing of the fibronectin EDA exon is essential for proper skin wound healing and normal lifespan. JCB 162: 149-160 [Abstract] [Full Text]  
• Hinz, B., Dugina, V., Ballestrem, C., Wehrle-Haller, B., Chaponnier, C. (2003). {alpha}-Smooth Muscle Actin Is Crucial for Focal Adhesion Maturation in Myofibroblasts. Mol. Biol. Cell 14: 2508-2519 [Abstract] [Full Text]  
• Eikmans, M., Baelde, H. J., Hagen, E. C., Paul, L. C., Eilers, P. H. C., de Heer, E., Bruijn, J. A. (2003). Renal mRNA Levels as Prognostic Tools in Kidney Diseases. J. Am. Soc. Nephrol. 14: 899-907 [Abstract] [Full Text]  
• Nony, P. A., Schnellmann, R. G. (2003). Mechanisms of Renal Cell Repair and Regeneration after Acute Renal Failure. J. Pharmacol. Exp. Ther. 304: 905-912 [Abstract] [Full Text]  
• Liao, Y.-F., Gotwals, P. J., Koteliansky, V. E., Sheppard, D., Van De Water, L. (2002). The EIIIA Segment of Fibronectin Is a Ligand for Integrins alpha 9beta 1 and alpha 4beta 1 Providing a Novel Mechanism for Regulating Cell Adhesion by Alternative Splicing. J. Biol. Chem. 277: 14467-14474 [Abstract] [Full Text]  
• Santas, A. J., Peterson, J. A., Halbleib, J. L., Craig, S. E., Humphries, M. J., Peters, D. M. P. (2002). Alternative Splicing of the IIICS Domain in Fibronectin Governs the Role of the Heparin II Domain in Fibrillogenesis and Cell Spreading. J. Biol. Chem. 277: 13650-13658 [Abstract] [Full Text]  
• Stepp, M. A., Gibson, H. E., Gala, P. H., Iglesia, D. D. Sta., Pajoohesh-Ganji, A., Pal-Ghosh, S., Brown, M., Aquino, C., Schwartz, A. M., Goldberger, O., Hinkes, M. T., Bernfield, M. (2002). Defects in keratinocyte activation during wound healing in the syndecan-1-deficient mouse. J. Cell Sci. 115: 4517-4531 [Abstract] [Full Text]  
• Yu, Y., Varughese, J., Brown, L. F., Mulliken, J. B., Bischoff, J. (2001). Increased Tie2 Expression, Enhanced Response to Angiopoietin-1, and Dysregulated Angiopoietin-2 Expression in Hemangioma-Derived Endothelial Cells. Am. J. Pathol. 159: 2271-2280 [Abstract] [Full Text]  
• Hinz, B., Mastrangelo, D., Iselin, C. E., Chaponnier, C., Gabbiani, G. (2001). Mechanical Tension Controls Granulation Tissue Contractile Activity and Myofibroblast Differentiation. Am. J. Pathol. 159: 1009-1020 [Abstract] [Full Text]  
• Hinz, B., Celetta, G., Tomasek, J. J., Gabbiani, G., Chaponnier, C. (2001). Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity. Mol. Biol. Cell 12: 2730-2741 [Abstract] [Full Text]  
• Zuk, A., Bonventre, J. V., Matlin, K. S. (2001). Expression of fibronectin splice variants in the postischemic rat kidney. Am. J. Physiol. Renal Physiol. 280: F1037-F1053 [Abstract] [Full Text]  
• Steffensen, B., Hakkinen, L., Larjava, H. (2001). Proteolytic Events of Wound-Healing -- Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules. CROBM 12: 373-398 [Abstract] [Full Text]  
• Coito, A. J., Onodera, K., Kato, H., Busuttil, R. W., Kupiec-Weglinski, J. W. (2000). Fibronectin-Mononuclear Cell Interactions Regulate Type 1 Helper T Cell Cytokine Network in Tolerant Transplant Recipients. Am. J. Pathol. 157: 1207-1218 [Abstract] [Full Text]  
• Davis, G. E., Bayless, K. J., Davis, M. J., Meininger, G. A. (2000). Regulation of Tissue Injury Responses by the Exposure of Matricryptic Sites within Extracellular Matrix Molecules. Am. J. Pathol. 156: 1489-1498 [Abstract] [Full Text]  
• Arbiser, J. L., Larsson, H., Claesson-Welsh, L., Bai, X., LaMontagne, K., Weiss, S. W., Soker, S., Flynn, E., Brown, L. F. (2000). Overexpression of VEGF 121 in Immortalized Endothelial Cells Causes Conversion to Slowly Growing Angiosarcoma and High Level Expression of the VEGF Receptors VEGFR-1 and VEGFR-2 in Vivo. Am. J. Pathol. 156: 1469-1476 [Abstract] [Full Text]  
• Saito, S., Yamaji, N., Yasunaga, K., Saito, T., Matsumoto, S.-i., Katoh, M., Kobayashi, S., Masuho, Y. (1999). The Fibronectin Extra Domain A Activates Matrix Metalloproteinase Gene Expression by an Interleukin-1-dependent Mechanism. J. Biol. Chem. 274: 30756-30763 [Abstract] [Full Text]  
• Liao, Y.-F., Wieder, K. G., Classen, J. M., De Water, L. V. (1999). Identification of Two Amino Acids within the EIIIA (ED-A) Segment of Fibronectin Constituting the Epitope for Two Function-blocking Monoclonal Antibodies. J. Biol. Chem. 274: 17876-17884 [Abstract] [Full Text]  
• Barnes, V. L., Musa, J., Mitchell, R. J., Barnes, J. L. (1999). Expression of Embryonic Fibronectin Isoform EIIIA Parallels {alpha}-Smooth Muscle Actin in Maturing and Diseased Kidney. J. Histochem. Cytochem. 47: 787-798 [Abstract] [Full Text]  
• Colman-Lerner, A., Fischman, M. L., Lanuza, G. M., Bissell, D. M., Kornblihtt, A. R., Barañao, J. L. (1999). Evidence for a Role of the Alternatively Spliced ED-I Sequence of Fibronectin during Ovarian Follicular Development. Endocrinology 140: 2541-2548 [Abstract] [Full Text]  
• Saren, A., Virkola, R., Hacker, J., Korhonen, T. K. (1999). The Cellular Form of Human Fibronectin as an Adhesion Target for the S Fimbriae of Meningitis-Associated Escherichia coli. Infect. Immun. 67: 2671-2676 [Abstract] [Full Text]  
• Brown, L. F., Guidi, A. J., Schnitt, S. J., Van De Water, L., Iruela-Arispe, M. L., Yeo, T.-K., Tognazzi, K., Dvorak, H. F. (1999). Vascular Stroma Formation in Carcinoma in Situ, Invasive Carcinoma, and Metastatic Carcinoma of the Breast. Clin. Cancer Res. 5: 1041-1056 [Abstract] [Full Text]  
• Barnes, J. L., Mitchell, R. J., Kanalas, J. J., Barnes, V. L. (1999). Differential Expression of Thrombospondin and Cellular Fibronectin During Remodeling in Proliferative Glomerulonephritis. J. Histochem. Cytochem. 47: 533-544 [Abstract] [Full Text]  
• Manabe, R.-i., Oh-e, N., Sekiguchi, K. (1999). Alternatively Spliced EDA Segment Regulates Fibronectin-dependent Cell Cycle Progression and Mitogenic Signal Transduction. J. Biol. Chem. 274: 5919-5924 [Abstract] [Full Text]  
• MEERSCHAERT, J., KELLY, E. A. B., MOSHER, D. F., BUSSE, W. W., JARJOUR, N. N. (1999). Segmental Antigen Challenge Increases Fibronectin in Bronchoalveolar Lavage Fluid. Am. J. Respir. Crit. Care Med. 159: 619-625 [Abstract] [Full Text]  
• Kumazaki, T, Mitsui, Y, Hamada, K, Sumida, H, Nishiyama, M (1999). Detection of alternative splicing of fibronectin mRNA in a single cell. J. Cell Sci. 112: 1449-1453 [Abstract]  
• Basile, D. P., Martin, D. R., Hammerman, M. R. (1998). Extracellular matrix-related genes in kidney after ischemic injury: potential role for TGF-beta in repair. Am. J. Physiol. Renal Physiol. 275: F894-F903 [Abstract] [Full Text]  
• Boesiger, J., Tsai, M., Maurer, M., Yamaguchi, M., Brown, L. F., Claffey, K. P., Dvorak, H. F., Galli, S. J. (1998). Mast Cells Can Secrete Vascular Permeability Factor/ Vascular Endothelial Cell Growth Factor and Exhibit Enhanced Release after Immunoglobulin E-dependent Upregulation of Fc{varepsilon} Receptor I Expression. JEM 188: 1135-1145 [Abstract] [Full Text]  
• Zuk, A., Bonventre, J. V., Brown, D., Matlin, K. S. (1998). Polarity, integrin, and extracellular matrix dynamics in the postischemic rat kidney. Am. J. Physiol. Cell Physiol. 275: C711-C731 [Abstract] [Full Text]  
• Serini, G., Bochaton-Piallat, M.-L., Ropraz, P., Geinoz, A., Borsi, L., Zardi, L., Gabbiani, G. (1998). The Fibronectin Domain ED-A Is Crucial for Myofibroblastic Phenotype Induction by Transforming Growth Factor-{beta}1. JCB 142: 873-881 [Abstract] [Full Text]  
• Maniscalco, W. M., Watkins, R. H., Chess, P. R., Sinkin, R. A., Horowitz, S., Toia, L. (1998). Cell-specific expression of fibronectin and EIIIA and EIIIB splice variants after oxygen injury. Am. J. Physiol. Lung Cell. Mol. Physiol. 274: L599-L609 [Abstract] [Full Text]  
• Verlander, J. W. (1998). Normal Ultrastructure of the Kidney and Lower Urinary Tract. Toxicol Pathol 26: 1-17 [Abstract]  
• Barnes, J. L. (1998). In Situ Hybridization in the Study of Remodeling in Proliferative Glomerulonephritis. Toxicol Pathol 26: 43-51 [Abstract]  
• George, E. L., Baldwin, H. S., Hynes, R. O. (1997). Fibronectins Are Essential for Heart and Blood Vessel Morphogenesis But Are Dispensable for Initial Specification of Precursor Cells. Blood 90: 3073-3081 [Abstract] [Full Text]  
• Manabe, R.-i., Oh-e, N., Maeda, T., Fukuda, T., Sekiguchi, K. (1997). Modulation of Cell-adhesive Activity of Fibronectin by the Alternatively Spliced EDA Segment. JCB 139: 295-307 [Abstract] [Full Text]  
• Martin, P. (1997). Wound Healing--Aiming for Perfect Skin Regeneration. Science 276: 75-81 [Abstract] [Full Text]  
• Hashimoto-Uoshima, M, Yan, Y., Schneider, G, Aukhil, I (1997). The alternatively spliced domains EIIIB and EIIIA of human fibronectin affect cell adhesion and spreading. J. Cell Sci. 110: 2271-2280 [Abstract]  
• Ellis, I, Banyard, J, Schor, S. (1997). Differential response of fetal and adult fibroblasts to cytokines: cell migration and hyaluronan synthesis. Development 124: 1593-1600 [Abstract]  
• Dubin, D., Peters, J. H., Brown, L. F., Logan, B., Kent, K. C., Berse, B., Berven, S., Cercek, B., Sharifi, B. G., Pratt, R. E., Dzau, V. J., Van De Water, L. (1995). Balloon Catheterization Induces Arterial Expression of Embryonic Fibronectins. Arterioscler. Thromb. Vasc. Bio. 15: 1958-1967 [Abstract] [Full Text]  
• Lukinmaa, P.-L., Vaheri, A. (1994). ED-A Region-containing Isoform of Cellular Fibronectin is Present in Dentin Matrix in Dentinogenesis Imperfecta Associated with Osteogenesis Imperfecta. JDR 73: 1187-1196 [Abstract]  
• Irwin, C., Picardo, M, Ellis, I, Sloan, P, Grey, A, McGurk, M, Schor, S. (1994). Inter- and intra-site heterogeneity in the expression of fetal-like phenotypic characteristics by gingival fibroblasts: potential significance for wound healing. J. Cell Sci. 107: 1333-1346 [Abstract]  
• George, E. L., Georges-Labouesse, E. N., Patel-King, R. S., Rayburn, H., Hynes, R. O. (1993). Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development 119: 1079-1091 [Abstract]  
• Dunlevy, J., Couchman, J. (1993). Controlled induction of focal adhesion disassembly and migration in primary fibroblasts. J. Cell Sci. 105: 489-500 [Abstract]  
• Mardon, H. J., Sebastio, G. (1992). Regulation of alternative splicing in the IIICS region of human fibronectin pre-mRNA encoding cell binding sites CS1 and CS5. J. Cell Sci. 103: 423-433 [Abstract]  
• Uitto, V.-J., Larjava, H., Peltonen, J., Brunette, D.M. (1992). Expression of Fibronectin and Integrins in Cultured Periodontal Ligament Epithelial Cells. JDR 71: 1203-1211 [Abstract]  
• Lefcort, F, Venstrom, K, McDonald, J., Reichardt, L. (1992). Regulation of expression of fibronectin and its receptor, alpha 5 beta 1, during development and regeneration of peripheral nerve. Development 116: 767-782 [Abstract]  
• Hynes, R.O., George, E.L., Georges, E.N., Guan, J.-L., Rayburn, H., Yang, J.T. (1992). Toward a Genetic Analysis of Cell-Matrix Adhesion. Cold Spring Harb Symp Quant Biol 57: 249-258 [Abstract]  
• Uitto, V.-J., Larjava, H. (1991). Extracellular Matrix Molecules and their Receptors: An Overview with Special Emphasis on Periodontal Tissues. CROBM 2: 323-354 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents