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We sought to define the role of cervical smooth muscle cells (CSMC) in normal and premature cervical remodeling (PCR). Specifically, we asked 1) if primary human CSMC secrete matrix metalloproteinases (MMPs; collagen remodeling enzymes), 2) if CSMC stretch induces MMP secretion, and 3) if CSMC stretch triggers increased MMP secretion in women with a history of PCR.
Using IRB approved protocols, CSMC were isolated from cervical tissue obtained prior to cerclage from 4 pregnant women (14-16wks) with a history of PCR resulting in preterm birth (PTB) <28 wks and 4 gestational-age matched controls (CTL) undergoing pregnancy termination. Immunocytochemistry for alpha-SMA, SM22 and desmin was used to identify smooth muscle cells (SMC). Cyclical stretch was applied (-13kpa, 15% elongation, 45s stretch, 15s release) for 24h using a Flexcell system and then MMP1, 2, 7, 9 and 10 concentrations in the basal media were determined by Luminex. Experiments were run in duplicate and statistical analyses included logistic regression, generalized estimated equation, ANOVA and Student’s t-test.
SMC markers were evident before and after 24h of cyclical stretch. At baseline, CSMC secrete MMPs, predominantly MMP1 and 2 with lower levels of MMP9 and 10 and cyclic stretch significantly increased MMP2 secretion in women with a history of PCR vs CTL (p=0.003, Figure 1).
Primary human CSMC secrete MMPs, which are thought to be critical for cervical remodeling. CSMC from pregnant women with a history of PCR secrete higher levels of MMP2 in response to stretch than CTL. This abnormal CSMC stretch response, characterized by increased MMP2 secretion, may elucidate a potential mechanism in the pathophysiology of PCR and PTB.