Title |
Extracellular matrix stiffness dictates Wnt expression through integrin pathway
|
---|---|
Published in |
Scientific Reports, February 2016
|
DOI | 10.1038/srep20395 |
Pubmed ID | |
Authors |
Jing Du, Yan Zu, Jing Li, Shuyuan Du, Yipu Xu, Lang Zhang, Li Jiang, Zhao Wang, Shu Chien, Chun Yang |
Abstract |
It is well established that extracellular matrix (ECM) stiffness plays a significant role in regulating the phenotypes and behaviors of many cell types. However, the mechanism underlying the sensing of mechanical cues and subsequent elasticity-triggered pathways remains largely unknown. We observed that stiff ECM significantly enhanced the expression level of several members of the Wnt/β-catenin pathway in both bone marrow mesenchymal stem cells and primary chondrocytes. The activation of β-catenin by stiff ECM is not dependent on Wnt signals but is elevated by the activation of integrin/ focal adhesion kinase (FAK) pathway. The accumulated β-catenin then bound to the wnt1 promoter region to up-regulate the gene transcription, thus constituting a positive feedback of the Wnt/β-catenin pathway. With the amplifying effect of positive feedback, this integrin-activated β-catenin/Wnt pathway plays significant roles in mediating the enhancement of Wnt signal on stiff ECM and contributes to the regulation of mesenchymal stem cell differentiation and primary chondrocyte phenotype maintenance. The present integrin-regulated Wnt1 expression and signaling contributes to the understanding of the molecular mechanisms underlying the regulation of cell behaviors by ECM elasticity. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | 20% |
Unknown | 4 | 80% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 2 | 40% |
Science communicators (journalists, bloggers, editors) | 1 | 20% |
Practitioners (doctors, other healthcare professionals) | 1 | 20% |
Scientists | 1 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 3 | 1% |
United States | 1 | <1% |
Germany | 1 | <1% |
Unknown | 249 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 79 | 31% |
Researcher | 35 | 14% |
Student > Master | 32 | 13% |
Student > Bachelor | 25 | 10% |
Student > Doctoral Student | 11 | 4% |
Other | 28 | 11% |
Unknown | 44 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 72 | 28% |
Agricultural and Biological Sciences | 45 | 18% |
Engineering | 31 | 12% |
Medicine and Dentistry | 20 | 8% |
Neuroscience | 5 | 2% |
Other | 28 | 11% |
Unknown | 53 | 21% |