Collagenases MMP-1, MMP-13, and Tissue Inhibitors TIMP-1, TIMP-2: Their Role in Healthy and Complicated Pregnancy and Potential as Preeclampsia Biomarkers-A Brief Review
APPLIED SCIENCES-BASEL
Authors: Nikolov, Asparuh; Popovski, Nikola; Hristova, Irena
Abstract
Extracellular matrix (ECM) turnover is characterized by a unique balance between matrix metalloproteinases' degradation activity and their natural inhibition by collagen specific tissue inhibitors. Human uterine ECM is a complex structure, majorly consisting of proteins as fibrillar collagen types I and III, fibronectin, and laminin. Collagenases are enzymes from the matrix metalloproteinases' family, which are predominantly involved in fibrillar collagen types I and III degradation. They are mainly represented by matrix metalloproteinase-1, -13 (MMP-1, -13), naturally inhibited by tissue inhibitors (TIMP-1, -2). The collagen structure of the uterus has been shown to be impaired in women with preeclampsia. This is a result of MMPs/TIMPs dysregulation interplay. This review article summarizes the actual available research data in the literature about the role of MMP-1, MMP-13 and TIMP-1, and TIMP-2 in collagen types I and III turnover in healthy and complicated pregnancy. Their potential use as circulating markers for diagnosis, prognosis, and monitoring of the development of preeclampsia is discussed as well.
Skullcapflavone II Inhibits Degradation of Type I Collagen by Suppressing MMP-1 Transcription in Human Skin Fibroblasts
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: Lee, Young Hun; Seo, Eun Kyoung; Lee, Seung-Taek
Abstract
Skullcapflavone II is a flavonoid derived from the root of Scutellaria baicalensis, a herbal medicine used for anti-inflammatory and anti-cancer therapies. We analyzed the effect of skullcapflavone II on the expression of matrix metalloproteinase-1 (MMP-1) and integrity of type I collagen in foreskin fibroblasts. Skullcapflavone II did not affect the secretion of type I collagen but reduced the secretion of MMP-1 in a dose- and time-dependent manner. Real-time reverse transcription-PCR and reporter gene assays showed that skullcapflavone II reduced MMP-1 expression at the transcriptional level. Skullcapflavone II inhibited the serum-induced activation of the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways required for MMP-1 transactivation. Skullcapflavone II also reduced tumor necrosis factor (TNF)--induced nuclear factor kappa light chain enhancer of activated B cells (NF-B) activation and subsequent MMP-1 expression. In three-dimensional culture of fibroblasts, skullcapflavone II down-regulated TNF--induced MMP-1 secretion and reduced breakdown of type I collagen. These results indicate that skullcapflavone II is a novel biomolecule that down-regulates MMP-1 expression in foreskin fibroblasts and therefore could be useful in therapies for maintaining the integrity of extracellular matrix.