Program in Molecular Medicine
Medical Subject Headings
Adherens Junctions; Animals; Cells, Cultured; Epidermis; Epithelial Cells; Humans; JNK Mitogen-Activated Protein Kinases; Keratinocytes; MAP Kinase Kinase 7; Mice; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase 9; Phosphorylation
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
We demonstrate that c-Jun N-terminal kinase (JNK) responds to substrate stiffness and regulates adherens junction (AJ) formation in epithelial cells in 2D cultures and in 3D tissues in vitro and in vivo. Rigid substrates led to JNK activation and AJ disassembly, whereas soft matrices suppressed JNK activity leading to AJ formation. Expression of constitutively active JNK (MKK7-JNK1) induced AJ dissolution even on soft substrates, whereas JNK knockdown (using shJNK) induced AJ formation even on hard substrates. In human epidermis, basal cells expressed phosphorylated JNK but lacked AJ, whereas suprabasal keratinocytes contained strong AJ but lacked phosphorylated JNK. AJ formation was significantly impaired even in the upper suprabasal layers of bioengineered epidermis when prepared with stiffer scaffold or keratinocytes expressing MKK7-JNK1. By contrast, shJNK1 or shJNK2 epidermis exhibited strong AJ even in the basal layer. The results with bioengineered epidermis were in full agreement with the epidermis of jnk1(-/-) or jnk2(-/-) mice. In conclusion, we propose that JNK mediates the effects of substrate stiffness on AJ formation in 2D and 3D contexts in vitro as well as in vivo.
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Citation: J Cell Sci. 2013 Jun 15;126(Pt 12):2718-29. doi: 10.1242/jcs.122903. Epub 2013 Apr 16. Link to article on publisher's site
Adherens junctions, Bioengineered epidermis, E-cadherin, β-catenin, Human primary keratinocytes, Intercellular interactions, Substrate rigidity, p-c-Jun
You, Hui; Padmashali, Roshan M.; Ranganathan, Aishwarya; Lei, Pedro; Girnius, Nomeda; Davis, Roger J.; and Andreadis, Stelios T., "JNK regulates compliance-induced adherens junctions formation in epithelial cells and tissues" (2013). Davis Lab. 6.