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Endothelial cell‑derived connective tissue growth factor stimulates fibroblast differentiation into myofibroblasts through integrin αVβ3

  • Authors:
    • Seo-Yeon Lee
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  • Published online on: November 24, 2022     https://doi.org/10.3892/etm.2022.11730
  • Article Number: 30
  • Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Connective tissue growth factor (CTGF) is expressed at high levels in blood vessels, where it functions as a regulator of a number of physiological processes, such as cell proliferation, angiogenesis and wound healing. In addition, CTGF has been reported to be involved in various pathological processes, such as tumor development and tissue fibrosis. However, one of the main roles of CTGF is to promote the differentiation of fibroblasts into myofibroblasts, a process that is involved in disease progression. Therefore, the present study aimed to investigate the possible mechanism by which pathological changes in the microvasculature can direct the activation of fibroblasts into myofibroblasts in the context of hypoxia/reoxygenation (H/R). Human umbilical vein endothelial cells (HUVECs) and normal human dermal fibroblasts were used in the present study. The expression levels of CTGF were determined by western blot analysis and reverse transcription‑semi‑quantitative PCR. To analyze the paracrine effect of HUVECs on fibroblasts, HUVECs were infected with CTGF‑expressing adenovirus and then the culture supernatant of HUVECs was collected to treat fibroblasts. The formation of α‑smooth muscle actin (α‑SMA) stress fibers in fibroblasts were observed by immunofluorescence staining. It was found that H/R significantly increased CTGF expression in HUVECs. CTGF was also able to directly induce the differentiation of fibroblasts into myofibroblasts. In addition, the culture supernatant from CTGF‑overexpressing HUVECs stimulated the formation of α‑SMA stress fibers in fibroblasts, which was inhibited by treatment with a functional blocking antibody against integrin αVβ3 and to a lesser degree by a blocking antibody against α6 integrin. The mechanism of CTGF upregulation by H/R in HUVECs was then evaluated, where it was found that the CTGF protein was more stable in the H/R group compared with that in the normoxic control group. These findings suggest that CTGF expressed and secreted by vascular endothelial cells under ischemia/reperfusion conditions can exert a paracrine influence on neighboring fibroblasts, which may in turn promote myofibroblast‑associated diseases. This association may hold potential as a therapeutic target.
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January-2023
Volume 25 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Lee S: Endothelial cell‑derived connective tissue growth factor stimulates fibroblast differentiation into myofibroblasts through integrin αVβ3. Exp Ther Med 25: 30, 2023
APA
Lee, S. (2023). Endothelial cell‑derived connective tissue growth factor stimulates fibroblast differentiation into myofibroblasts through integrin αVβ3. Experimental and Therapeutic Medicine, 25, 30. https://doi.org/10.3892/etm.2022.11730
MLA
Lee, S."Endothelial cell‑derived connective tissue growth factor stimulates fibroblast differentiation into myofibroblasts through integrin αVβ3". Experimental and Therapeutic Medicine 25.1 (2023): 30.
Chicago
Lee, S."Endothelial cell‑derived connective tissue growth factor stimulates fibroblast differentiation into myofibroblasts through integrin αVβ3". Experimental and Therapeutic Medicine 25, no. 1 (2023): 30. https://doi.org/10.3892/etm.2022.11730