Extracellular Matrix Stiffness and Composition Regulate the Myofibroblast Differentiation of Vaginal Fibroblasts

International Journal of Molecular Sciences

ManonH. Kerkhof¹  ChristianE. H. Schmelzer²  Cindy van de Westerlo-van Rijt³  AlejandraM. Ruiz-Zapata³  KirstenB. Kluivers³  Andrea Heinz⁴  Egbert Oosterwijk⁵  Reinout Stoop⁶ 

[1] Curilion, Women’s Health Centre, 2015 BJ Haarlem, The Netherlands;Department of Biological and Macromolecular Materials, Fraunhofer Institute for Microstructure Materials and Systems IMWS, 06120 Halle (Saale), Germany;Department of Obstetrics and Gynecology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;Department of Pharmacy, LEO Foundation Center for Cutaneous Drug Delivery, University of Copenhagen, 2100 Copenhagen, Denmark;Department of Urology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands;TNO Metabolic Health Research, 2301 DA Leiden, The Netherlands;

关键词: alpha-smooth muscle actin;    cell culture system;    collagen;    decellularized tissues;    extracellular matrix;    matrix stiffness;   

DOI  :  10.3390/ijms21134762

来源: DOAJ

【 摘 要 】

Fibroblast to myofibroblast differentiation is a key feature of wound-healing in soft tissues, including the vagina. Vaginal fibroblasts maintain the integrity of the vaginal wall tissues, essential to keep pelvic organs in place and avoid pelvic organ prolapse (POP). The micro-environment of vaginal tissues in POP patients is stiffer and has different extracellular matrix (ECM) composition than healthy vaginal tissues. In this study, we employed a series of matrices with known stiffnesses, as well as vaginal ECMs, in combination with vaginal fibroblasts from POP and healthy tissues to investigate how matrix stiffness and composition regulate myofibroblast differentiation in vaginal fibroblasts. Stiffness was positively correlated to production of α-smooth muscle actin (α-SMA). Vaginal ECMs induced myofibroblast differentiation as both α-SMA and collagen gene expressions were increased. This differentiation was more pronounced in cells seeded on POP-ECMs that were stiffer than those derived from healthy tissues and had higher collagen and elastin protein content. We showed that stiffness and ECM content regulate vaginal myofibroblast differentiation. We provide preliminary evidence that vaginal fibroblasts might recognize POP-ECMs as scar tissues that need to be remodeled. This is fundamentally important for tissue repair, and provides a rational basis for POP disease modelling and therapeutic innovations in vaginal reconstruction.

【 授权许可】

Unknown