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

doi:10.1371/journal.pone.0193456

	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
刊名	PLOS ONE
	2018-04-09
卷号	13 期号:4 页码:e0193456
ISSN号	1932-6203
DOI	10.1371/journal.pone.0193456
英文摘要	To 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.
分类号	二类/Q1
URL标识	查看原文
WOS关键词	STRESS URINARY-INCONTINENCE ; GENE-EXPRESSION ; BIOMECHANICAL PROPERTIES ; CANCER BIOLOGY ; DECORIN ; FIBROMODULIN ; LUMICAN ; FIBRILLOGENESIS ; BIGLYCAN ; BINDING
WOS研究方向	Multidisciplinary Sciences
语种	英语
WOS记录号	WOS:000429505000002
资助机构	National Key Technology Research and Development Program during the 11th Five-Year Plan Period [2007BAI04B05]
内容类型	期刊论文
源URL	[http://dspace.imech.ac.cn/handle/311007/77818]
专题	力学研究所_国家微重力实验室
作者单位	1.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
推荐引用方式 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.