Gene expressions of small leucine-rich repeat proteoglycans and fibulin-5 are decreased in pelvic organ prolapse.
Few studies are performed on the sustainability of the pelvic floor extracellular matrix important for preventing development of pelvic organ prolapse (POP). Collagens I and III, the elastin-associated proteins fibrillin-1 and fibulin-5 and the small leucine-rich repeat proteoglycans (SLRPs) decorin, lumican and fibromodulin are involved in giving the tissue its mechanical properties. Para-urethral biopsies were obtained from 15 women, 6 pre- and 9 post-menopausal, with POP. Real-time reverse transcription-polymerase chain reaction and immunohistochemistry for collagen I, collagen III, fibrillin-1, fibulin-5, decorin, lumican and fibromodulin were performed and compared with 14 controls, 8 pre- and 6 post-menopausal. Statistical comparisons controlled for age changes in gene expressions. A 16-fold decrease in decorin mRNA expression, P = 0.0001, and 8-fold in lumican mRNA expression, P = 0.001, were discovered in premenopausal POP compared with matched controls. In all women with POP, there were lower gene expressions of fibromodulin, P = 0.004, and fibulin-5, P = 0.001, compared with all controls. All proteins were detectable by immunohistochemistry, showing a weaker staining for decorin in premenopausal POP. For the first time, we show substantially decreased gene signal for production of SLRPs, regulators of collagen fiber assembly and impairment in elastic fiber assembly by down-regulation of fibulin-5 in POP.
Söderberg
Marie Westergren
MW
Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital Solna, Södersjukhuset, S-171 76 Stockholm, Sweden. marie.westergren-soderberg@sodersjukhuset.se
Byström
Birgitta
B
Kalamajski
Sebastian
S
Malmström
Anders
A
Ekman-Ordeberg
Gunvor
G
D000328:Adult; D000368:Aged; D000818:Animals; D001706:Biopsy; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000090263:Leucine-Rich Repeat Proteins; D008593:Menopause; D008875:Middle Aged; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014782:Visceral Prolapse / Q000235:genetics*
D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins; D011509:Proteoglycans; D012333:RNA, Messenger