Transcriptional Regulation of Connective Tissue Metabolism Genes in Women With Pelvic Organ Prolapse
| العنوان: | Transcriptional Regulation of Connective Tissue Metabolism Genes in Women With Pelvic Organ Prolapse |
|---|---|
| المؤلفون: | Nathan Kow, Ali Borazjani, Beri Ridgeway, Samantha Harris, Margot S. Damaser |
| المصدر: | Female Pelvic Medicine & Reconstructive Surgery. 23:44-52 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adult, 0301 basic medicine, medicine.medical_specialty, Receptors, Peptide, Urology, H&E stain, Gene Expression, Connective tissue, Matrix (biology), Collagen Type I, Pelvic Organ Prolapse, Statistics, Nonparametric, Article, Bone morphogenetic protein 1, Bone Morphogenetic Protein 1, Receptors, G-Protein-Coupled, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Gene expression, medicine, Humans, Tissue Inhibitor of Metalloproteinase-3, Relaxin, Tissue Inhibitor of Metalloproteinase-2, 030219 obstetrics & reproductive medicine, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Obstetrics and Gynecology, Middle Aged, Extracellular Matrix, Up-Regulation, Postmenopause, Collagen Type III, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Premenopause, Connective Tissue, Connective tissue metabolism, Case-Control Studies, Matrix Metalloproteinase 2, Regression Analysis, Surgery, business |
| الوصف: | Objective The aim of this study was to compare differences in expressions and relationships between key genes involved in extracellular matrix metabolism and tissue cellularity in women with and without pelvic organ prolapse (POP). Methods A total of 80 biopsies (anterior cuff, posterior cuff, and/or leading edge) were obtained from 30 women: n = 10 premenopausal without POP (controls), n = 10 premenopausal with POP, and n = 10 postmenopausal with POP. Quantitative reverse-transcriptase polymerase chain reaction was used to assess gene expression of bone morphogenetic protein 1 (BMP1), collagen types I (COL1) and III (COL3), relaxin family peptide receptor 1 (RXFP1), matrix metallopeptidase 2, and TIMP metallopeptidase inhibitors 2 and 3. Hematoxylin and eosin staining was used to assess cellularity of the connective tissue layer. Kruskal-Wallis test, Mann-Whitney U test, Pearson correlation, or linear regression analyses were used, as appropriate. Results Bone morphogenetic protein 1 expression was significantly up-regulated in patients with POP compared with controls. Bone morphogenetic protein 1 expression was correlated with COL1 expression in all groups but only correlated with TIMP metallopeptidase inhibitor 3 expression in controls. Similarly, COL3 expression was correlated with RXFP1 expression in women with POP but not in controls. The degree of dependence (slope of the regression line) between COL1 and COL3 expressions was significantly elevated in premenopausal women with POP compared with the other 2 groups. The slopes between COL1-COL3, COL3-matrix metallopeptidase 2, COL1-RXFP1, and COL3-RXFP1 expressions were significantly lower in postmenopausal women compared with premenopausal women with POP. No differences were found in overall tissue cellularity. Conclusions Bone morphogenetic protein 1 expression may play a significant role in the pathophysiology of POP. The finding that BMP1 expression was correlated with COL1 expression in all groups suggests a conserved association between BMP1 and collagen synthesis in the vaginal wall. The elevated slope between COL1 and COL3 expressions may be associated with early (premenopausal) development of POP. The expression of RXFP1 in postmenopausal women and its altered intergene regulation suggests a role for RXFP1 in connective tissue metabolism outside pregnancy. |
| تدمد: | 2151-8378 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce486a2f7fd7c04b9651f8640836da3cTest https://doi.org/10.1097/spv.0000000000000337Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ce486a2f7fd7c04b9651f8640836da3c |
| قاعدة البيانات: | OpenAIRE |
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term="%22Surgery%22">Surgery</searchLink><br /><searchLink fieldCode="DE" term="%22business%22">business</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => Objective The aim of this study was to compare differences in expressions and relationships between key genes involved in extracellular matrix metabolism and tissue cellularity in women with and without pelvic organ prolapse (POP). Methods A total of 80 biopsies (anterior cuff, posterior cuff, and/or leading edge) were obtained from 30 women: n = 10 premenopausal without POP (controls), n = 10 premenopausal with POP, and n = 10 postmenopausal with POP. Quantitative reverse-transcriptase polymerase chain reaction was used to assess gene expression of bone morphogenetic protein 1 (BMP1), collagen types I (COL1) and III (COL3), relaxin family peptide receptor 1 (RXFP1), matrix metallopeptidase 2, and TIMP metallopeptidase inhibitors 2 and 3. Hematoxylin and eosin staining was used to assess cellularity of the connective tissue layer. Kruskal-Wallis test, Mann-Whitney U test, Pearson correlation, or linear regression analyses were used, as appropriate. Results Bone morphogenetic protein 1 expression was significantly up-regulated in patients with POP compared with controls. Bone morphogenetic protein 1 expression was correlated with COL1 expression in all groups but only correlated with TIMP metallopeptidase inhibitor 3 expression in controls. Similarly, COL3 expression was correlated with RXFP1 expression in women with POP but not in controls. The degree of dependence (slope of the regression line) between COL1 and COL3 expressions was significantly elevated in premenopausal women with POP compared with the other 2 groups. The slopes between COL1-COL3, COL3-matrix metallopeptidase 2, COL1-RXFP1, and COL3-RXFP1 expressions were significantly lower in postmenopausal women compared with premenopausal women with POP. No differences were found in overall tissue cellularity. Conclusions Bone morphogenetic protein 1 expression may play a significant role in the pathophysiology of POP. The finding that BMP1 expression was correlated with COL1 expression in all groups suggests a conserved association between BMP1 and collagen synthesis in the vaginal wall. 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