| Changes in transcription profile and cytoskeleton morphology in pelvic ligament fibroblasts in response to stretch: the effects of estradiol and levormeloxifene. | |
| | |
MedLine Citation:
|
PMID: 18184756 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Failure of ligamentous support of the genital tract to resist intra-abdominal pressure is a plausible underlying mechanism for the development of pelvic organ prolapse, but the nature of the molecular response of pelvic tissue support remains unknown. We hypothesized that the expression of genes coding for proteins involved in maintaining the cellular and extracellular integrity would be altered as a result of mechanical stretch. Therefore, cDNA microarrays were used to examine the difference in transcriptional profile in RNA of primary culture fibroblasts subjected to mechanical stretch and those that remained static. Out of 34 mechano-responsive genes identified (P < 0.05), four were coding for regulation of actin cytoskeleton remodelling, and its interaction with the extracellular matrix proteins; these are phosphatidyl inositol-4-phosphate 5-kinase (PIP5K1C), the human signal-induced proliferation associated gene-1 (SIPA-1), TNFRSF1A-associated via death domain (TRADD) and deoxyribonuclease 1-like 1 (DNase 1-L1). The transcriptosomal changes led us to investigate the phenotypic consequences of stretch, levormeloxifene and estradiol (E(2)) on the cytoskeleton of cultured fibroblasts. The percentage of cells with abnormal F-actin configuration was significantly higher in fibroblasts subjected to stretch compared with the static model (P < 0.0001). Levormeloxifene caused similar significant alterations in actin morphology of the static fibroblasts. The use of E(2) did not reverse the process or protect the cells from the effect of stretch, but significantly increased the rate of fibroblast proliferation, suggestive of a role in healing process. Mechanical stretch and/or levormeloxifene disturb the fibroblasts ability to maintain the cytoskeleton architecture and we speculate that they may disrupt ligamentous integrity and result in clinical prolapse. |
| | |
Authors:
|
Ayman A A Ewies; Mona Elshafie; Jin Li; Adrian Stanley; John Thompson; Jerry Styles; Ian White; Farook Al-Azzawi |
Related Documents
:
|
16990566 - Rock controls matrix synthesis in vascular smooth muscle cells: coupling vasoconstricti... 20929926 - Electrical stimulation inhibits neointimal hyperplasia after abdominal aorta balloon in... 17907296 - Regulation of activin receptor-interacting protein 2 expression in mouse hepatoma hepa1... 16865716 - Denervation alters mrna levels of repair-associated genes in a rabbit medial collateral... 3778466 - Expression of the fibrinogen genes in rat megakaryocytes. 7744246 - Lxr, a nuclear receptor that defines a distinct retinoid response pathway. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-01-09 |
Journal Detail:
|
Title: Molecular human reproduction Volume: 14 ISSN: 1460-2407 ISO Abbreviation: Mol. Hum. Reprod. Publication Date: 2008 Feb |
Date Detail:
|
Created Date: 2008-02-19 Completed Date: 2008-07-15 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9513710 Medline TA: Mol Hum Reprod Country: England |
Other Details:
|
Languages: eng Pagination: 127-35 Citation Subset: IM |
Affiliation:
|
Department of Gynaecology, The Ipswich Hospital, Ipswich, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Actins
/
genetics,
metabolism Blotting, Western Cell Proliferation / drug effects Cells, Cultured Estradiol / pharmacology* Fibroblasts / cytology, drug effects*, metabolism Gene Expression Profiling* Humans Ligaments / cytology* Oligonucleotide Array Sequence Analysis Pelvis Pyrrolidines / pharmacology* Stress, Mechanical Transcription, Genetic / drug effects Tubulin / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Actins; 0/Pyrrolidines; 0/Tubulin; 50-28-2/Estradiol; 78994-23-7/levormeloxifene |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The role of lactate in the exercise-induced human growth hormone response: evidence from McArdle dis...
Next Document: Chemotherapy-induced pica and anorexia are reduced by common hepatic branch vagotomy in the rat.