Denervation-induced skeletal muscle fibrosis is mediated by CTGF/CCN2 independently of TGF-beta

Matrix Biology

dc.creatorRebolledo, Daniela L
dc.creatorGonzález-Figueroa, David Andrés
dc.creatorFaúndez-Contreras, Jennifer
dc.creatorContreras, Osvaldo
dc.creatorVio, Carlos P
dc.creatorMurphy-Ullrich, Joanne E
dc.creatorLipson, Kenneth E
dc.creatorBrandan-Siqués, Enrique Héctor
dc.date2021-08-23T22:58:00Z
dc.date2022-07-07T02:43:18Z
dc.date2021-08-23T22:58:00Z
dc.date2022-07-07T02:43:18Z
dc.date2019
dc.date.accessioned2023-08-22T07:31:46Z
dc.date.available2023-08-22T07:31:46Z
dc.identifier1150106
dc.identifier1150106
dc.identifierhttps://hdl.handle.net/10533/252177
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8331800
dc.descriptionMuscular fibrosis is caused by excessive accumulation of extracellular matrix (ECM) that replaces functional tissue, and it is a feature of several myopathies and neuropathies. Knowledge of the biology and regulation of pro-fibrotic factors is critical for the development of new therapeutic strategies. Upon unilateral sciatic nerve transection, we observed accumulation of ECM proteins such as collagen and fibronectin in the denervated hindlimb, together with increased levels of the profibrotic factors transforming growth factor type beta (TGF-beta) and connective tissue growth factor (CTGF/CCN2). In mice hemizygous for CTGF/CCN2 or in mice treated with a blocking antibody against CTGF/CCN2, we observed reduced accumulation of ECM proteins after denervation as compared to control mice, with no changes in fibro/adipogenic progenitors (FAPs), suggesting a direct role of CTGF/CCN2 on denervation-induced fibrosis. During time course experiments, we observed that ECM proteins and CTGF/CCN2 levels are increased early after denervation (2-4 days), while TGF-beta signaling shows a delayed kinetics of appearance (1-2 weeks). Furthermore, blockade of TGF-beta signaling does not decrease fibronectin or CTGF levels after 4 days of denervation. These results suggest that in our model CTGF/CCN2 is not up-regulated by canonical TGF-beta signaling early after denervation and that other factors are likely involved in the early fibrotic response following skeletal muscle denervation. (C) 2019 Elsevier B.V. All rights reserved.
dc.descriptionRegular 2015
dc.descriptionFONDECYT
dc.descriptionFONDECYT
dc.languageeng
dc.relationhandle/10533/111557
dc.relationhandle/10533/111541
dc.relationhandle/10533/108045
dc.relationhttps://www.academia.edu/34234423/Narcoseries_mujeres_poderosas_y_machos_sensibles
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsinfo:eu-repo/semantics/article
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleDenervation-induced skeletal muscle fibrosis is mediated by CTGF/CCN2 independently of TGF-beta
dc.titleMatrix Biology
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/publishedVersion


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