Premium
Activated Fibroblasts are Required for Extracellular Matrix Remodeling in the Human Cervix
Author(s) -
Malmström A,
EkmanOrdeberg G
Publication year - 2005
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2005.130117q.x
Subject(s) - extracellular matrix , fibroblast , matrix metalloproteinase , andrology , in vivo , microbiology and biotechnology , cytokine , biology , interleukin 6 , secretion , cervix , immunohistochemistry , in vitro , endocrinology , immunology , medicine , biochemistry , cancer , genetics
The normal ripening of the human cervix is characterized by rapid degradation of the extracellular matrix, where fibroblasts play an important role. To accomplish this, the fibroblasts undergo phenotypic changes, generally characterized by decreased synthesis of ECM molecules and increased production of degrading enzymes. The hypothesis of this study is that fibroblasts from cervices at different stages of remodeling are of different phenotypes. Fibroblasts were obtained from nonpregnant women, women after 36 weeks of pregnancy and women directly after partus (postpartal) and kept for at least three–four passages to obtain stable conditions prior experiments were performed. The cells were immunostained for differentiation markers, screened for cytokine and MMP expression and production, followed by a global proteomic search. In accordance with in vivo data, a decrease of α‐smooth muscle actin and 4‐prolyl‐hydroxylase was noted by immunohistochemical staining with time of pregnancy. The fibroblasts established from postpartal donors had a three‐ to fourfold increase of interleukin 6 (IL‐6). The production of the chemotactic interleukin 8 (IL‐6) was increased even further, five‐ to sixfold, in postpartal fibroblast cultures. This correlates well to the events in vivo, where IL‐6 and Il‐8 is produced in high amounts by cervical fibroblast. In addition also the secretion metalloproteinase 1 and 3 are increased threefold in postpartal cultures, which is in agreement with in vivo events. Intermediate amounts of interleukins and metalloproteinases are produced in culture obtained after 36 weeks of pregnancy. A global proteomic approach resulted in regulated proteins involved in Ca‐signaling, cytoskeletal mobility and apoptosis. Taken together these data suggest that remodeling of cervix is achieved by a transient activation or recruitment or differentiation of active fibroblasts usually found in inflammatory conditions, characterized by increased MMP and cytokine expression.