Abstract
Preterm premature rupture of membranes (pPROM) is a major cause of preterm birth. Recently, extracellular matrix-directed treatment is applied for wound healing. Here, we used a pregnant mouse model to test the efficacy of collagen type 1 gel for healing of the prematurely ruptured fetal membranes. Although injection of PBS into the ruptured fetal membranes resulted in 40% closure, injection of collagen type 1 improved closure rates to 90% within 72 h. Macrophages of the M2 wound healing phenotype were entrapped in the collagen layer. In primary human amnion mesenchymal cells, collagen type 1 gels activated collagen receptor discoidin domain receptor 2 (DDR2) to induce myosin light chain phosphorylation and migration of injured amnion mesenchymal cells. These findings define the mechanisms for matrix-directed therapeutics for pPROM.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amnion / cytology
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Animals
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Cell Movement / drug effects
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Collagen Type I / pharmacology
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Collagen Type I / therapeutic use*
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Discoidin Domain Receptor 2 / antagonists & inhibitors
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Discoidin Domain Receptor 2 / genetics
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Discoidin Domain Receptor 2 / metabolism
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Disease Models, Animal
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Female
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Fetal Membranes, Premature Rupture / drug therapy*
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Gels / chemistry
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Humans
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Macrophages / cytology
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Macrophages / metabolism
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Mesenchymal Stem Cells / cytology
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Mesenchymal Stem Cells / drug effects
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Mesenchymal Stem Cells / metabolism
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Mice
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Myosin Light Chains / metabolism
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Phosphorylation / drug effects
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Pregnancy
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RNA Interference
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RNA, Small Interfering / metabolism
Substances
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Collagen Type I
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Gels
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Myosin Light Chains
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RNA, Small Interfering
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DDR2 protein, human
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Discoidin Domain Receptor 2
Supplementary concepts
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Preterm Premature Rupture of the Membranes