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Uptake and intracellular transport of the connective tissue growth factor: a potential mode of action
Abstract
Connective tissue growth factor (CTGF) is a secreted cysteine-rich protein now considered as an important effector molecule in both physiological and pathological processes. An increasing amount of evidence indicates that CTGF plays a key role in the pathogenesis of different fibrotic disorders including diabetic nephropathy. However, the molecular mechanisms by which CTGF exerts its effects are not known. Here we provide the first evidence for the existence of an intracellular transport pathway for the growth factor in human mesangial cells. Our results demonstrate that CTGF is internalized from the cell surface in endosomes and accumulates in a juxtanuclear organelle from which the growth factor is then translocated into the cytosol. In the cytosol CTGF is phosphorylated by protein kinase C and PMA treatment can enhance this phosphorylation. Phosphorylated CTGF may have an important role in the cytosol, but it is also translocated into the nucleus where it may directly affect transcription.
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CTGF can be internalized into cytosol by human mesangial cells and exert protective effect against diabetic nephropathy.
“In support of this possibility, CTGF can be internalized into the cytosol by human mesangial cells and exert its protective effect against diabetic nephropathy (51).”
From Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia (2017) · cites this paper as [51]
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- Kim, H. S., Nagalla, S. R., Oh, Y., Wilson, E., Roberts, Jr, C. T. and Rosenfeld, R. G. (1997) Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs) : characterization of connective tissue growth factor as a member of the IGFBP superfamily. Proc. Natl. Acad. Sci. U.S.A. 94, 12981-12986
- Marzluff, W. F. and Huang, R. C. C. (1985) Transcription of RNA in isolated nuclei. In Transcription and Translation : A Practical Approach (Hames, B. D. and Higgins, S. J., eds.), pp. 89-129, IRL Press, Oxford 30
- Moll, T., Tebb, G., Surana, U., Robitsch, H. and Nasmyth, K. (1991) The role of phosphorylation and the CDC28 protein kinase in cell cycle-regulated nuclear import of the S. cerevisiae transcription factor SWI5. Cell (Cambridge, Mass.) 66, 743-758 Received 5 February 2001/29 May 2001 ; accepted 16 July 2001
- Moroianu, J. and Riordan, J. F. (1994) Nuclear translocation of angiogenin in proliferation endothelial cells is essential to its angiogenic activity. Proc. Natl. Acad. Sci. U.S.A. 90, 1677-1681
- Kimura, H. (1994) Schwannoma-derived growth factor must be transported into the nucleus to exert its mitogenic activity. Proc. Natl. Acad. Sci. U.S.A. 90, 2165-2169
- Mason, I. J. (1994) The ins and outs of fibroblast growth factors. Cell (Cambridge, Mass.) 78, 547-552
- Wiedlocha, A., Falnes, P. O., Madshus, I. H., Sandvig, K. and Olsnes, S. (1994) Dual mode of signal transduction by externally added acidic fibroblast growth factor. Cell (Cambridge, Mass.) 76, 1039-1051
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Metadata
- Authors
- WAHAB, N. A., BRINKMAN, H., & MASON, R. M.
- Affiliations
- Cell and Molecular Biology Section, Division of Biomedical Sciences, Imperial College School of Medicine, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London SW7 2AZ, U.K.
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2001-09-24
- Volume
- 359
- Issue
- 1
- Pages
- 89-97
- ISSN
- 0264-6021
- 1470-8728
- Cited by
- 64
- References
- 0
- Language
- en
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