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Journal of Biomedical Research | Volume: 29
November 19-20, 2018 | Paris, France
Molecular Biology, Tissue Science and Regenerative Medicine
International Conference on
Joint Event
&
4
th
World Heart Congress
CTGF/CCN2 a profibrotic factor to target in neuromuscular diseases
Enrique Brandan
Pontificia Universidad Católica de Chile, Chile
M
uscular fibrosis is an excessive accumulation of
extracellular matrix (ECM) replacing functional tissue,
characteristic of several myopathies and neuropathies. The
knowledgeofpro-fibrotic factorsbiologyandregulation iscritical
to develop new therapeutic strategies. Upon unilateral sciatic
section, we observe in denervated hindlimb accumulation of
ECM proteins such as collagen and fibronectin together with
an increase of profibrotic factors TGFβ and CTGF/CCN2. We
use hemizygous mice for CTGF/CCN2 and treatments with a
blocking antibody against CTGF/CCN2 and we observe reduced
denervation-induced fibrosis when compared to control mice
suggesting a direct role for CTGF/CCN2 on denervation-induced
fibrosis. In time course experiments, we observe that ECM
proteins and CTGF/ levels are increased early after denervation
(2-4 days), while TGFβ signalling present a delayed kinetics
of appearance (1-2 weeks). Furthermore, blockage of TGFβ
signalling does not decrease fibronectin or CTGF levels 4 days
after denervation. These results suggest that inourmodel CTGF/
CCN2 is not up-regulated by canonical TGFβ signalling early
after denervation and other factors might be involved in the
fibrotic response very soon after skeletal muscle denervation.
e:
ebrandan@bio.puc.clMolecular Biology & Heart Congress 2018, Volume 29
DOI: 10.4066/biomedicalresearch-C8-023