Hydrogels preserve native phenotypes of valvular fibroblasts through an elasticity-regulated PI3K/AKT pathway
Abstract
Valvular interstitial cells (VICs) are the principal cellular component of cardiac valves and maintain normal valve homeostasis. During valvular fibrosis, VICs differentiate into myofibroblasts and stiffen the valve matrix. The results in this report demonstrate that standard techniques of culturing VICs on supraphysiologically stiff, tissue-culture polystyrene cause a dramatic induction of myofibroblast differentiation. In contrast, culturing VICs on soft, poly(ethylene glycol)-based hydrogels preserves the native, quiescent phenotype. A detailed study of VIC mechano-sensing reveals that matrix elasticity elicits pathologic changes in VICs through PI3K/AKT signaling. A more complete understanding of the molecular mechanisms of VIC mechano-biology may facilitate development of novel therapeutics targeting downstream signaling in matrix-stiffness-associated diseases, and may be applicable to fibrotic diseases in different tissues.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- November 2013
- DOI:
- 10.1073/pnas.1306369110
- Bibcode:
- 2013PNAS..11019336W