Wound Healing and Surgical Planning
Alexander Berlin in Mohs and Cutaneous Surgery, 2014
The main function of fibroblasts in a healing wound is the synthesis of components of the ECM, including collagen, glycosaminoglycans (GAGs) and proteoglycans, and elastin. This function is induced by several mediators, including TGF-β and connective tissue growth factor (CTGF).50 CTGF itself is released by fibroblasts in response to macrophage-derived TGF-β1 and may act in an autocrine fashion to stimulate further chemotaxis and proliferation of fibroblasts, as well as new collagen production.43,51,52 Fibrinogen matrix serves as the scaffold for new collagen deposition. Initially, fibroblasts preferentially synthesize type III, or fetal-like, collagen. Type III collagen exhibits a smaller fibril diameter and less cross-linking than type I collagen, the predominant type in adult skin.53 Collagen type switching occurs later in the wound healing process, during remodeling, as discussed in the section “Remodeling Phase.”
Pathogenesis
Aparna Palit, Arun C. Inamadar in Systemic Sclerosis, 2019
CTGF demonstrates functions similar to TGF-β. Increased expression of CTGF in lesioned tissues of patients with SSc is mediated by TGF-β, hypoxia and ET-1. A variation in the promoter region of CTGF gene, which predisposes an individual to develop SSc, has been demonstrated.3 TGF-β stimulates FBs, vascular smooth muscles, and endothelial cells to secrete CTGF. Through the autocrine loop stimulation, CTGF maintains a continuous and prolonged cycle of fibrosis by stimulating its own production.1 The expression of another important growth factor, PDGF, is involved in fibrosis and endothelial injury and has been known to increase in the lungs, skin, and bronchoalveolar lavage fluid of SSC patients. PDGF promotes endothelial proliferation, ECM production, and the release of profibrotic mediators like IL-6 and MCP-1. The autocrine PDGF/PDGFRα signaling loop in FBs is dependent on TGF-β and IL-1α.3
Management of idiopathic pulmonary fibrosis
Muhunthan Thillai, David R Moller, Keith C Meyer in Clinical Handbook of Interstitial Lung Disease, 2017
Connective tissue growth factor (CTGF) is a matricellular protein that can play roles in epithelial–mesenchymal transition, activation of myofibroblasts, remodelling of extracellular matrix and stimulation of TGF-β release (160). In mouse models, inhibition of CTGF not only reduced, but could even reverse the fibrotic effects of radiation (161). FG-3019, an inhibitor of CTGF, has been trialed in human subjects with IPF in an open-label study (162). Twenty percent of patients experienced reduction in fibrotic load, as measured by CT scanning. Further placebo-controlled RCTs are required to confirm these findings, and, if successful, to identify and validate stratifying factors associated with differences in response (163).
Selenium, a dietary-antioxidant with cardioprotective effects, prevents the impairments in heart rate and systolic blood pressure in adolescent rats exposed to binge drinking treatment
Published in The American Journal of Drug and Alcohol Abuse, 2021
M Luisa Ojeda, Paula Sobrino, Rui Manuel Rua, María del Carmen Gallego-Lopez, Fátima Nogales, Olimpia Carreras
The intermittent BD pattern used in adolescent rats increased all of the vascular markers studied herein. VEGF is considered the most potent proangiogenic growth factor involved in vascular permeability, vascular dilation, endothelial proliferation and angiogenesis. Previous data established that acute ethanol exposure significantly increases serum VEGF values, but also perturbs endothelial VEGF signaling and action (50,51). The growth factor CTGF plays important roles in cell adhesion, migration, proliferation, and angiogenesis and is critically involved in fibrotic process. Also, different studies have related CTGF to VEGF production and angiogenesis (52). CTGF is upregulated by stimuli involved in cardiovascular damage, including OS (53). Since ethanol exposure increases OS, both proteins (CTGF and VEGF) increased in the present study and endothelial function is compromised. Se supplementation improves vascular function, lowering SBP values by decreasing both parameters to normal values, probably due to its antioxidant properties. The observation of beneficial actions of Se on vascular function are not new, since anti-atherosclerotic activity of Se has been described previously (21).
A key role of microRNA-26a in the scar formation after glaucoma filtration surgery
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Wei-Hong Wang, Ai-Jun Deng, Sheng-Guang He
CTGF is one of the most important downstream cytokines of TGF pathway and it exists widely in many kinds of human organs [26]. The biological effects of CTGF were quite widely abundant. In general, CTGF could promote mitosis, improve proliferation, induce chemotaxis, increase cell adhesion, promote ECM synthesis, and function as a key growth factor in the wound healing and tissue repair processes [11,27]. Besides, as a major profibrotic molecule downstream of the TGF-β signalling pathway, CTGF is considered a key factor in differentiation of fibroblasts into MFs and in ECM synthesis [10]. Very low or no expression of CTGF in normal condition, but it was overexpressed in pathological conditions. The overexpression of CTGF is closely related with the occurrence of some proliferative or fibrous disease. There is a certain relationship such as pathological scar, keloid, scleroderma, liver cirrhosis, atherosclerosis, pulmonary fibrosis, renal fibrosis and tumour and migration. Thus, CTGF is considered to be a switch and biological marker for the initiation of fibrosis [28]. In addition, CTGF also has the function of inducing phenotypic transformation in some tissues. All these reveal the important role and key role of CTGF in fibrosis and scar formation. In this study, it was found that activation of miR-26a could suppress expression of CTGF significantly and thus miR-26a produced the potential role in the drug development for filtering tract maintenance.
Perspectives on the advances in the pharmacotherapeutic management of Duchenne muscular dystrophy
Published in Expert Opinion on Pharmacotherapy, 2022
Kelsie D. Kracht, Nicole L. Eichorn, Daniel J. Berlau
Pamrevlumab is a monoclonal antibody that inhibits connective tissue growth factor (CTGF) to reduce fibrosis. CTGF has many roles, but of note, it mediates tissue remodeling and fibrosis. Fibrosis is a concern in the heart and lungs in DMD patients because it contributes to cardiomyopathy and loss of pulmonary function as the disease progresses. Preliminary data from the phase 2 trial, where it is assessing change in percent predicted forced vital capacity (ppFVC), gave enough evidence of preserved limb strength and improved heart and lung function for the FDA to fast track the medication (ClinicalTrials.gov identifier: NCT02606136) [81]. Pamrevlumab is being evaluated in phase 3 trials LELANTOS with the primary outcome of change in score of PUL from baseline and LELANTOS-2, evaluating the change in NSAA (ClinicalTrials.gov identifiers NCT04371666, NCT04632940). Pamrevlumab is expected to be evaluated for FDA approval in the next few years.
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