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Involvement of CTGF in TGF-beta1-stimulation of myofibroblast differentiation and collagen matrix contraction in the presence of mechanical stress.
Invest Ophthalmol Vis Sci. 2004 Apr; 45(4):1109-16.IO

Abstract

PURPOSE

This study was undertaken to investigate the role of connective tissue growth factor (CTGF) in fibroblast-to-myofibroblast differentiation and fibroblast-mediated collagen matrix contraction in the presence of mechanical stress.

METHODS

An in vitro three-dimensional contraction model of human corneal-fibroblast-seeded collagen lattices (FSCLs) in the presence of mechanical stress generated by attaching the lattices to the culture well was used to measure FSCL contraction. FSCLs were treated with CTGF; TGF-beta1; serum-free (SF) control medium; or TGF-beta1 plus antisense oligodeoxynucleotides to CTGF; TGF-beta1 plus scrambled-sequence oligodeoxynucleotide to CTGF; or TGF-beta antibody. Expression of alpha-smooth muscle actin (alpha-SMA) by fibroblasts in FSCLs was detected by immunostaining and confocal microscopy, whereas ELISA was used for the fibroblasts cultured on plastic. The conditioned media were analyzed by ELISA for CTGF production.

RESULTS

Exogenous CTGF stimulated significantly less collagen matrix contraction and myofibroblast differentiation than TGF-beta1, but similar to that stimulated by SF. TGF-beta1 stimulated fibroblasts to express CTGF. CTGF antisense oligodeoxynucleotide inhibited TGF-beta1-stimulated myofibroblast differentiation and FSCL contraction. Exogenous CTGF circumvented the inhibitory effects of CTGF antisense on FSCL contraction. TGF-beta antibody significantly inhibited FSCL contraction and myofibroblast differentiation under mechanical stress and SF control conditions.

CONCLUSIONS

In the presence of mechanical stress, CTGF is necessary for TGF-beta1-stimulation of myofibroblast differentiation and subsequent collagen matrix contraction, but CTGF alone is not sufficient to induce myofibroblast differentiation and collagen matrix contraction. Thus, TGF-beta1 appears to regulate multiple genes that are essential for fibroblast-mediated contraction of stressed matrix, one of which is CTGF.

Authors+Show Affiliations

Wound Healing Research Unit, Institute of Ophthalmology, London, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15037576

Citation

Garrett, Qian, et al. "Involvement of CTGF in TGF-beta1-stimulation of Myofibroblast Differentiation and Collagen Matrix Contraction in the Presence of Mechanical Stress." Investigative Ophthalmology & Visual Science, vol. 45, no. 4, 2004, pp. 1109-16.
Garrett Q, Khaw PT, Blalock TD, et al. Involvement of CTGF in TGF-beta1-stimulation of myofibroblast differentiation and collagen matrix contraction in the presence of mechanical stress. Invest Ophthalmol Vis Sci. 2004;45(4):1109-16.
Garrett, Q., Khaw, P. T., Blalock, T. D., Schultz, G. S., Grotendorst, G. R., & Daniels, J. T. (2004). Involvement of CTGF in TGF-beta1-stimulation of myofibroblast differentiation and collagen matrix contraction in the presence of mechanical stress. Investigative Ophthalmology & Visual Science, 45(4), 1109-16.
Garrett Q, et al. Involvement of CTGF in TGF-beta1-stimulation of Myofibroblast Differentiation and Collagen Matrix Contraction in the Presence of Mechanical Stress. Invest Ophthalmol Vis Sci. 2004;45(4):1109-16. PubMed PMID: 15037576.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of CTGF in TGF-beta1-stimulation of myofibroblast differentiation and collagen matrix contraction in the presence of mechanical stress. AU - Garrett,Qian, AU - Khaw,Peng T, AU - Blalock,Timothy D, AU - Schultz,Gregory S, AU - Grotendorst,Gary R, AU - Daniels,Julie T, PY - 2004/3/24/pubmed PY - 2004/4/21/medline PY - 2004/3/24/entrez SP - 1109 EP - 16 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 45 IS - 4 N2 - PURPOSE: This study was undertaken to investigate the role of connective tissue growth factor (CTGF) in fibroblast-to-myofibroblast differentiation and fibroblast-mediated collagen matrix contraction in the presence of mechanical stress. METHODS: An in vitro three-dimensional contraction model of human corneal-fibroblast-seeded collagen lattices (FSCLs) in the presence of mechanical stress generated by attaching the lattices to the culture well was used to measure FSCL contraction. FSCLs were treated with CTGF; TGF-beta1; serum-free (SF) control medium; or TGF-beta1 plus antisense oligodeoxynucleotides to CTGF; TGF-beta1 plus scrambled-sequence oligodeoxynucleotide to CTGF; or TGF-beta antibody. Expression of alpha-smooth muscle actin (alpha-SMA) by fibroblasts in FSCLs was detected by immunostaining and confocal microscopy, whereas ELISA was used for the fibroblasts cultured on plastic. The conditioned media were analyzed by ELISA for CTGF production. RESULTS: Exogenous CTGF stimulated significantly less collagen matrix contraction and myofibroblast differentiation than TGF-beta1, but similar to that stimulated by SF. TGF-beta1 stimulated fibroblasts to express CTGF. CTGF antisense oligodeoxynucleotide inhibited TGF-beta1-stimulated myofibroblast differentiation and FSCL contraction. Exogenous CTGF circumvented the inhibitory effects of CTGF antisense on FSCL contraction. TGF-beta antibody significantly inhibited FSCL contraction and myofibroblast differentiation under mechanical stress and SF control conditions. CONCLUSIONS: In the presence of mechanical stress, CTGF is necessary for TGF-beta1-stimulation of myofibroblast differentiation and subsequent collagen matrix contraction, but CTGF alone is not sufficient to induce myofibroblast differentiation and collagen matrix contraction. Thus, TGF-beta1 appears to regulate multiple genes that are essential for fibroblast-mediated contraction of stressed matrix, one of which is CTGF. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/15037576/Involvement_of_CTGF_in_TGF_beta1_stimulation_of_myofibroblast_differentiation_and_collagen_matrix_contraction_in_the_presence_of_mechanical_stress_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.03-0660 DB - PRIME DP - Unbound Medicine ER -