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Age-Dependent Expression of Collagen Receptors and Deformation of Type I Collagen Substrates by Rat Cardiac Fibroblasts

  • Christopher G. Wilson (a1), John W. Stone (a2), Vennece Fowlkes (a1), Mary O. Morales (a1), Catherine J. Murphy (a3), Sarah C. Baxter (a4) and Edie C. Goldsmith (a1)...

Abstract

Little is known about how age influences the ways in which cardiac fibroblasts interact with the extracellular matrix. We investigated the deformation of collagen substrates by neonatal and adult rat cardiac fibroblasts in monolayer and three-dimensional (3D) cultures, and quantified the expression of three collagen receptors [discoidin domain receptor (DDR)1, DDR2, and β1 integrin] and the contractile protein alpha smooth muscle actin (α-SMA) in these cells. We report that adult fibroblasts contracted 3D collagen substrates significantly less than their neonate counterparts, whereas no differences were observed in monolayer cultures. Adult cells had lower expression of β1 integrin and α-SMA than neonate cultures, and we detected significant correlations between the expression of α-SMA and each of the collagen receptors in neonate cells but not in adult cells. Consistent with recent work demonstrating age-dependent interactions with myocytes, our results indicate that interactions between cardiac fibroblasts and the extracellular matrix change with age.

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Corresponding author

Corresponding author. E-mail: edie.goldsmith@uscmed.sc.edu

References

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Arora, P.D. & McCulloch, C.A. (1994). Dependence of collagen remodelling on alpha-smooth muscle actin expression by fibroblasts. J Cell Physiol 159, 161175.
Arora, P.D., Narani, N. & McCulloch, C.A. (1999). The compliance of collagen gels regulates transforming growth factor-beta induction of alpha-smooth muscle actin in fibroblasts. Am J Pathol 154, 871882.
Banerjee, I., Fuseler, J.W., Price, R.L., Borg, T.K. & Baudino, T.A. (2007). Determination of cell types and numbers during cardiac development in the neonatal and adult rat and mouse. Am J Physiol Heart Circ Physiol 293, H1883H1891.
Baudino, T.A., Carver, W., Giles, W. & Borg, T.K. (2006). Cardiac fibroblasts: Friend or foe? Am J Physiol Heart Circ Physiol 291, H1015H1026.
Baxter, S.C., Morales, M.O. & Goldsmith, E.C. (2008). Adaptive changes in cardiac fibroblast morphology and collagen organization as a result of mechanical environment. Cell Biochem Biophys 51, 3344.
Burgess, M.L., Carver, W.E., Terracio, L., Wilson, S.P., Wilson, M.A. & Borg, T.K. (1994). Integrin-mediated collagen gel contraction by cardiac fibroblasts. Effects of angiotensin II. Circ Res 74, 291298.
Carver, W., Molano, I., Reaves, T.A., Borg, T.K. & Terracio, L. (1995). Role of the alpha 1 beta 1 integrin complex in collagen gel contraction in vitro by fibroblasts. J Cell Physiol 165, 425437.
Chan, M.W., Arora, P.D., Bozavikov, P. & McCulloch, C.A. (2009). FAK, PIP5KIgamma and gelsolin cooperatively mediate force-induced expression of alpha-smooth muscle actin. J Cell Sci 122, 27692781.
Cukierman, E., Pankov, R., Stevens, D.R. & Yamada, K.M. (2001). Taking cell-matrix adhesions to the third dimension. Science 294, 17081712.
Engler, A., Bacakova, L., Newman, C., Hategan, A., Griffin, M. & Discher, D. (2004). Substrate compliance versus ligand density in cell on gel responses. Biophys J 86, 617628.
Engler, A.J., Carag-Krieger, C., Johnson, C.P., Raab, M., Tang, H.Y., Speicher, D.W., Sanger, J.W., Sanger, J.M. & Discher, D.E. (2008). Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: Scar-like rigidity inhibits beating. J Cell Sci 121, 37943802.
Engler, A.J., Sen, S., Sweeney, H.L. & Discher, D.E. (2006). Matrix elasticity directs stem cell lineage specification. Cell 126, 677689.
Fernandez, P. & Bausch, A.R. (2009). The compaction of gels by cells: A case of collective mechanical activity. Integr Biol (Camb) 1, 252259.
Flamant, M., Placier, S., Rodenas, A., Curat, C.A., Vogel, W.F., Chatziantoniou, C. & Dussaule, J.C. (2006). Discoidin domain receptor 1 null mice are protected against hypertension-induced renal disease. J Am Soc Nephrol 17, 33743381.
Goldsmith, E.C., Hoffman, A., Morales, M.O., Potts, J.D., Price, R.L., McFadden, A., Rice, M. & Borg, T.K. (2004). Organization of fibroblasts in the heart. Dev Dyn 230, 787794.
Goldsmith, E.C., Zhang, X., Watson, J., Hastings, J. & Potts, J.D. (2010). The collagen receptor DDR2 is expressed during early cardiac development. Anat Rec (Hoboken) 293(5), 762769.
Grove, D., Zak, R., Nair, K.G. & Aschenbrenner, V. (1969). Biochemical correlates of cardiac hypertrophy. IV. Observations on the cellular organization of growth during myocardial hypertrophy in the rat. Circ Res 25, 473485.
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, 27302741.
Hou, G., Vogel, W.F. & Bendeck, M.P. (2002). Tyrosine kinase activity of discoidin domain receptor 1 is necessary for smooth muscle cell migration and matrix metalloproteinase expression. Circ Res 90, 11471149.
Ieda, M., Tsuchihashi, T., Ivey, K.N., Ross, R.S., Hong, T.T., Shaw, R.M. & Srivastava, D. (2009). Cardiac fibroblasts regulate myocardial proliferation through beta1 integrin signaling. Dev Cell 16, 233244.
Jana, N.R., Gearheart, L. & Murphy, C.J. (2001a). Seed-mediated growth approach for shape-controlled synthesis of spheroidal and rod-like gold nanoparticles using a surfactant template. Adv Mater 13, 13891393.
Jana, N.R., Gearheart, L. & Murphy, C.J. (2001b). Wet chemical synthesis of high aspect ratio cylindrical gold nanorods. J Phys Chem B 105, 40654067.
Knezevic, V., Sim, A.J., Borg, T.K. & Holmes, J.W. (2002). Isotonic biaxial loading of fibroblast-populated collagen gels: A versatile, low–cost system for the study of mechanobiology. Biomech Model Mechanobiol 1, 5967.
Lijnen, P., Petrov, V. & Fagard, R. (2003). Transforming growth factor-beta 1-mediated collagen gel contraction by cardiac fibroblasts. J Renin Angiotensin Aldosterone Syst 4, 113118.
Matsuyama, W., Watanabe, M., Shirahama, Y., Oonakahara, K., Higashimoto, I., Yoshimura, T., Osame, M. & Arimura, K. (2005). Activation of discoidin domain receptor 1 on CD14-positive bronchoalveolar lavage fluid cells induces chemokine production in idiopathic pulmonary fibrosis. J Immunol 174, 64906498.
Morales, M.O., Price, R.L. & Goldsmith, E.C. (2005). Expression of discoidin domain receptor 2 (DDR2) in the developing heart. Microsc Microanal 11, 260267.
Olaso, E., Ikeda, K., Eng, F.J., Xu, L., Wang, L.H., Lin, H.C. & Friedman, S.L. (2001). DDR2 receptor promotes MMP-2-mediated proliferation and invasion by hepatic stellate cells. J Clin Invest 108, 13691378.
Olaso, E., Labrador, J.P., Wang, L., Ikeda, K., Eng, F.J., Klein, R., Lovett, D.H., Lin, H.C. & Friedman, S.L. (2002). 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 277, 36063613.
Orendorff, C.J., Baxter, S.C., Goldsmith, E.C. & Murphy, C.J. (2005). Light scattering from gold nanorods: Tracking material deformation. Nanotechnology 16, 16012605.
Pfaffl, M.W. (2001). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29, e45.
Sadoshima, J. & Izumo, S. (1993). Molecular characterization of angiotensin II–induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype. Circ Res 73, 413423.
Stone, J.W., Sisco, P.N., Goldsmith, E.C., Baxter, S.C. & Murphy, C.J. (2007). Using gold nanorods to probe cell-induced collagen deformation. Nano Lett 7, 116119.
Villarreal, F.J., Kim, N.N., Ungab, G.D., Printz, M.P. & Dillmann, W.H. (1993). Identification of functional angiotensin II receptors on rat cardiac fibroblasts. Circulation 88, 28492861.
Vogel, W., Brakebusch, C., Fässler, R., Alves, F., Ruggiero, F. & Pawson, T. (2000). Discoidin domain receptor 1 is activated independently of beta(1) integrin. J Biol Chem 275, 57795784.
Weber, K.T. & Brilla, C.G. (1993). Structural basis for pathologic left ventricular hypertrophy. Clin Cardiol 16, II10II14.
Weber, K.T., Sun, Y., Tyagi, S.C. & Cleutjens, J.P. (1994). Collagen network of the myocardium: Function, structural remodeling and regulatory mechanisms. J Mol Cell Cardiol 26, 279292.
Wilson, C.G., Sisco, P.N., Goldsmith, E.C. & Murphy, C.J. (2009). Glycosaminoglycan-functionalized gold nanorods: Interactions with cardiac cells and type I collagen. J Mater Chem 19, 63326340.
Xu, L., Peng, H., Wu, D., Hu, K., Goldring, M.B., Olsen, B.R. & Li, Y. (2005). Activation of the discoidin domain receptor 2 induces expression of matrix metalloproteinase 13 associated with osteoarthritis in mice. J Biol Chem 280, 548555.

Keywords

Age-Dependent Expression of Collagen Receptors and Deformation of Type I Collagen Substrates by Rat Cardiac Fibroblasts

  • Christopher G. Wilson (a1), John W. Stone (a2), Vennece Fowlkes (a1), Mary O. Morales (a1), Catherine J. Murphy (a3), Sarah C. Baxter (a4) and Edie C. Goldsmith (a1)...

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