Cellular Mechanics of Primary Human Cervical Fibroblasts: Influence of Progesterone and a Pro-inflammatory Cytokine.
Vasudha ShuklaVictoria BarnhouseWilliam E AckermanTaryn L SummerfieldHeather M PowellJennifer L LeightDouglas A KnissSamir N GhadialiPublished in: Annals of biomedical engineering (2017)
The leading cause of neonatal mortality, pre-term birth, is often caused by pre-mature ripening/opening of the uterine cervix. Although cervical fibroblasts play an important role in modulating the cervix's extracellular matrix (ECM) and mechanical properties, it is not known how hormones, i.e., progesterone, and pro-inflammatory insults alter fibroblast mechanics, fibroblast-ECM interactions and the resulting changes in tissue mechanics. Here we investigate how progesterone and a pro-inflammatory cytokine, IL-1β, alter the biomechanical properties of human cervical fibroblasts and the fibroblast-ECM interactions that govern tissue-scale mechanics. Primary human fibroblasts were isolated from non-pregnant cervix and treated with estrogen/progesterone, IL-1β or both. The resulting changes in ECM gene expression, matrix remodeling, traction force generation, cell-ECM adhesion and tissue contractility were monitored. Results indicate that IL-1β induces a significant reduction in traction force and ECM adhesion independent of pre-treatment with progesterone. These cell level effects altered tissue-scale mechanics where IL-1β inhibited the contraction of a collagen gel over 6 days. Interestingly, progesterone treatment alone did not modulate traction forces or gel contraction but did result in a dramatic increase in cell-ECM adhesion. Therefore, the protective effect of progesterone may be due to altered adhesion dynamics as opposed to altered ECM remodeling.
Keyphrases
- extracellular matrix
- estrogen receptor
- endothelial cells
- gene expression
- single cell
- wound healing
- cell therapy
- induced pluripotent stem cells
- pluripotent stem cells
- biofilm formation
- preterm birth
- dna methylation
- single molecule
- smooth muscle
- type diabetes
- pregnant women
- gestational age
- cardiovascular disease
- preterm infants
- stem cells
- pseudomonas aeruginosa
- cell migration
- risk factors
- cardiovascular events
- cystic fibrosis
- hyaluronic acid
- pregnancy outcomes