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Effects of mechanical stretching on the morphology of extracellular polymers and the mRNA expression of collagens and small leucine-rich repeat proteoglycans in vaginal fibroblasts from women with pelvic organ prolapse
Wang SM; Lv DY(吕东媛); Zhang ZY; Jia XY; Yang L
Source PublicationPLOS ONE
2018-04-09
Volume13Issue:4Pages:e0193456
ISSN1932-6203
AbstractTo determine the effect of mechanical stretching load and the efficacy of postmenopausal estrogen therapy (ET) on pelvic organ prolapse (POP), vaginal fibroblasts isolated from postmenopausal women with or without POP were subjected to 0.1-Hz uniaxial cyclic mechanical stretching (CS) with 10% elongation and 10-8 M 17-I3-estradiol (E-2) treatment. We investigated the morphological characteristics of extracellular polymers using scanning electron microscopy (SEM) and monitored the mRNA expression of type I collagen (COL I) and type III collagen (COL III) as well as the small leucine-rich proteoglycan (SLRP) family members decorin (DCN), biglycan (BGN), fibromodulin (FMO), and lumican (LUM), using real-time quantitative polymerase chain reaction (RT-PCR). Using SEM, certain viscoelastic polymers were found to be randomly distributed among fibroblasts, which for normal fibroblasts formed clusters of plum flower-like patterns under static-culture conditions and resembled stretched strips when stretched in culture, whereas polymers among POP fibroblasts resembled stretched strips under static-cultured conditions and presented broken networks when stretched in culture. RT-PCR revealed that COL I, DCN, BGN, FMO, and LUM mRNA expression was significantly higher in POP than in normal fibroblasts under static-culture condition. Following CS, COL I and BGN mRNA expression was significantly up-regulated in normal fibroblasts, and DCN and FMO mRNA expression was down-regulated in POP fibroblasts. Following concomitant CS and E2 treatment, significantly elevated COL I and DCN mRNA expression was observed in normal fibroblasts, and significantly elevated COL I and BGN mRNA expression was observed in POP fibroblasts. COL III mRNA expression was not significantly different between the POP and normal group, and CS did not significantly affect expression in either group, though COL III was down-regulated in normal fibroblasts concomitantly treated with E-2 and CS. We conclude that the morphological distribution of extracellular polymers in POP fibroblasts exhibited higher sensitivity and lower tolerance to stretching loads than do normal fibroblasts. These mechanical properties were further reflected in the transcription of COL I. Defects in the compensatory function of BGN for DCN and LUM for FMO exist in POP fibroblasts, which further affect the structure and function of COL I in response to stretching load, ultimately resulting in abnormal reconstruction of pelvic supportive connective tissues and the occurrence of POP. ET can maintain stretching-induced elevations in COL I and DCN transcription in healthy women and improve stretching-induced COL I, DCN, BGN, and FMO transcriptional changes in POP women to prevent and improve POP. Only down-regulated COL III transcription was observed upon concomitant CS and E2 treatment in normal fibroblasts, which suggests that the tensile strength, not the elasticity, of the supportive connective tissues is damaged in POP and that the higher tensile strength induced by ET in healthy fibroblasts prevents POP. These findings confirm the role of higher sensitivity and lower tolerance to mechanical stretching in the pathogenesis of POP and further provide evidence supporting the use of ET to prevent and inhibit POP in postmenopausal women.
DOI10.1371/journal.pone.0193456
URL查看原文
Indexed BySCI
Language英语
WOS IDWOS:000429505000002
WOS KeywordSTRESS URINARY-INCONTINENCE ; GENE-EXPRESSION ; BIOMECHANICAL PROPERTIES ; CANCER BIOLOGY ; DECORIN ; FIBROMODULIN ; LUMICAN ; FIBRILLOGENESIS ; BIGLYCAN ; BINDING
WOS Research AreaMultidisciplinary Sciences
WOS SubjectScience & Technology - Other Topics
Funding OrganizationNational Key Technology Research and Development Program during the 11th Five-Year Plan Period [2007BAI04B05]
Classification二类/Q1
Ranking2
Citation statistics
Document Type期刊论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/77818
Collection国家微重力实验室
Affiliation1.Capital Med Univ, Beijing Chaoyang Hosp, Dept Obstet & Gynecol, Beijing, Peoples R China
2.Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Key Lab Micrograv,Natl Micrograv Lab, Beijing, Peoples R China
3.Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, Beijing, Peoples R China
4.Capital Med Univ, Beijing Chaoyang Hosp, Med Res Ctr, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Wang SM,Lv DY,Zhang ZY,et al. Effects of mechanical stretching on the morphology of extracellular polymers and the mRNA expression of collagens and small leucine-rich repeat proteoglycans in vaginal fibroblasts from women with pelvic organ prolapse[J]. PLOS ONE,2018,13(4):e0193456.
APA Wang SM,吕东媛,Zhang ZY,Jia XY,&Yang L.(2018).Effects of mechanical stretching on the morphology of extracellular polymers and the mRNA expression of collagens and small leucine-rich repeat proteoglycans in vaginal fibroblasts from women with pelvic organ prolapse.PLOS ONE,13(4),e0193456.
MLA Wang SM,et al."Effects of mechanical stretching on the morphology of extracellular polymers and the mRNA expression of collagens and small leucine-rich repeat proteoglycans in vaginal fibroblasts from women with pelvic organ prolapse".PLOS ONE 13.4(2018):e0193456.
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