CCN2 Increases TGF-β Receptor Type II Expression in Vascular Smooth Muscle Cells: Essential Role of CCN2 in the TGF-β Pathway Regulation
| Autor: | Antonio Tejera-Muñoz, Laura Marquez-Exposito, Lucía Tejedor-Santamaría, Sandra Rayego-Mateos, Macarena Orejudo, Beatriz Suarez-Álvarez, Carlos López-Larrea, Marta Ruíz-Ortega, Raúl R. Rodrigues-Díez |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
TGF-β
Male QH301-705.5 EGFR Myocytes Smooth Muscle Smad Proteins Models Biological Catalysis Article Muscle Smooth Vascular Inorganic Chemistry Transforming Growth Factor beta Animals RNA Messenger Biology (General) Physical and Theoretical Chemistry TGF-β receptors Phosphorylation QD1-999 Molecular Biology Spectroscopy Aorta integumentary system Organic Chemistry Connective Tissue Growth Factor Receptor Transforming Growth Factor-beta Type II CCN2 SMAD CTGF General Medicine Computer Science Applications ErbB Receptors Mice Inbred C57BL Chemistry Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 375 International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 23, Iss 375, p 375 (2022) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23010375 |
| Popis: | The cellular communication network factor 2 (CCN2/CTGF) has been traditionally described as a mediator of the fibrotic responses induced by other factors including the transforming growth factor β (TGF-β). However, several studies have defined a direct role of CCN2 acting as a growth factor inducing oxidative and proinflammatory responses. The presence of CCN2 and TGF-β together in the cellular context has been described as a requisite to induce a persistent fibrotic response, but the precise mechanisms implicated in this relation are not described yet. Considering the main role of TGF-β receptors (TβR) in the TGF-β pathway activation, our aim was to investigate the effects of CCN2 in the regulation of TβRI and TβRII levels in vascular smooth muscle cells (VSMCs). While no differences were observed in TβRI levels, an increase in TβRII expression at both gene and protein level were found 48 h after stimulation with the C-terminal fragment of CCN2 (CCN2(IV)). Cell pretreatment with a TβRI inhibitor did not modify TβRII increment induced by CCN2(VI), demonstrating a TGF-β-independent response. Secondly, CCN2(IV) rapidly activated the SMAD pathway in VSMCs, this being crucial in the upregulation of TβRII since the preincubation with an SMAD3 inhibitor prevented it. Similarly, pretreatment with the epidermal growth factor receptor (EGFR) inhibitor erlotinib abolished TβRII upregulation, indicating the participation of this receptor in the observed responses. Our findings suggest a direct role of CCN2 maintaining the TGF-β pathway activation by increasing TβRII expression in an EGFR-SMAD dependent manner activation. |
| Databáze: | OpenAIRE |
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