AI Article Synopsis
- CCN2 is crucial for osteoblast differentiation and function, stimulated by TGF-β1, with a lesser-known role for AFAP1 in this process.
- AFAP1 expression in osteoblasts varies, peaking as cells proliferate and again during mineralization, and is upregulated by TGF-β1.
- The study shows that AFAP1 is necessary for Src activation and CCN2 induction in response to TGF-β1, suggesting it plays a key role in producing extracellular matrix components like collagen XIIa.
Article Abstract
Background: CCN2 acts as an anabolic growth factor to regulate osteoblast differentiation and function. CCN2 is induced by TGF-β1 and acts as a mediator of TGF-β1 induced matrix production in osteoblasts and Src is required for CCN2 induction by TGF-β1; however, the molecular mechanisms that control CCN2 induction in osteoblasts are poorly understood. AFAP1 binds activated forms of Src and can direct the activation of Src in certain cell types, however a role for AFAP1 downstream of TGF-β1 or in osteoblats is undefined. In this study, we investigated the role of AFAP1 for CCN2 induction by TGF-β1 in primary osteoblasts.
Results: We demonstrated that AFAP1 expression in osteoblasts occurs in a biphasic pattern with maximal expression levels occurring during osteoblast proliferation (~day 3), reduced expression during matrix production/maturation (~day 14-21), an a further increase in expression during mineralization (~day 21). AFAP1 expression is induced by TGF-β1 treatment in osteoblasts during days 7, 14 and 21. In osteoblasts, AFAP1 binds to Src and is required for Src activation by TGF-β1 and CCN2 promoter activity and protein induction by TGF-β1 treatment was impaired using AFAP1 siRNA, indicating the requirement of AFAP1 for CCN2 induction by TGF-β1. We also demonstrated that TGF-β1 induction of extracellular matrix protein collagen XIIa occurs in an AFAP1 dependent fashion.
Conclusions: This study demonstrates that AFAP1 is an essential downstream signaling component of TGF-β1 for Src activation, CCN2 induction and collagen XIIa in osteoblasts.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560384 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136712 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Extracellular matrix protein 1 binds to connective tissue growth factor against liver fibrosis and ductular reaction.
Hepatol Commun
November 2024
Department of Pathology, Tulane University, New Orleans, Louisiana, USA.
Background: Extracellular matrix protein 1 (ECM1) can inhibit TGFβ activation, but its antifibrotic action remains largely unknown. This study aims to investigate ECM1 function and its physical interaction with the profibrotic connective tissue growth factor (CTGF) in fibrosis and ductular reaction (DR).
Methods: Ecm1 knockouts or animals that ectopically expressed this gene were subjected to induction of liver fibrosis and DR by feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or α-naphthyl-isothiocyanate (ANIT).
Exogenous S1P via S1P receptor 2 induces CTGF expression through Src-RhoA-ROCK-YAP pathway in hepatic stellate cells.
Mol Biol Rep
September 2024
Department of Health Science and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-Ro, Gangnam-Gu, Seoul, 06351, South Korea.
Article Synopsis
- Hepatic fibrosis is a chronic liver condition driven by excessive extracellular matrix production, where hepatic stellate cells (HSCs) are activated by inflammatory factors like sphingosine 1-phosphate (S1P).
- The study explored how S1P affects YAP activation in HSCs, utilizing various methods to reveal that S1P receptor 2 (S1PR2) is crucial for this process and that it activates the Hippo signaling pathway, leading to the expression of fibrosis-related genes.
- Findings indicate that the S1P/S1PR2 signaling pathway could be a potential therapeutic target for treating hepatic fibrosis, as it significantly influences the production of key proteins involved in the
The novel thromboxane prostanoid receptor mediates CTGF production to drive human nasal fibroblast self-migration through NF-κB and PKCδ-CREB signaling pathways.
J Cell Physiol
September 2024
School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
Chronic rhinosinusitis without nasal polyp (CRSsNP) is characterized by tissue repair/remodeling and the subepithelial stroma region in whose nasal mucosa has been reported by us to have thromboxane A (TXA) prostanoid (TP) receptor and overexpress connective tissue growth factor (CTGF). Therefore, this study aimed to investigate the relationship between TP receptor activation and CTGF production/function in human CRSsNP nasal mucosa stromal fibroblasts. We found that TP agonists including U46619 and IBOP ([1S-[1α,2α(Z),3β(1E,3 S*),4α]]-7-[3-[3-hydroxy-4-(4-iodophenoxy)-1-butenyl]-7-oxabicyclo[2.
View Article and Find Full Text PDFThe pro-fibrotic effects of glucocorticoids may lead to a suboptimal therapeutic response for vocal fold (VF) pathology. Targeting macrophage-fibroblast interactions is an interesting therapeutic strategy; macrophages alter their phenotype to mediate both inflammation and fibrosis. In the current study, we investigated concentration-dependent effects of methylprednisolone on the fibrotic response, with an emphasis on YAP/TAZ-TEAD signaling, and inflammatory gene expression in VF fibroblasts in physical contact with macrophages.
View Article and Find Full Text PDFThe matricellular protein CCN5 prevents anti-VEGF drug-induced epithelial-mesenchymal transition of retinal pigment epithelium.
Sci Rep
June 2024
College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, Korea.
Article Synopsis
- * The study discovered that anti-VEGF drugs like bevacizumab, ranibizumab, and aflibercept promote epithelial-mesenchymal transition (EMT) in retinal cells, increasing the levels of CCN2, a pro-fibrotic factor.
- * Co-treatment with CCN5, which inhibits CCN2, mitigated the negative effects of anti-VEGF drugs, indicating that targeting these pathways could improve treatment outcomes for nAMD.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!