Extracellular matrix metabolism disorder induced by mechanical strain on human parametrial ligament fibroblasts.
Pelvic organ prolapse (POP) is a global health problem that may seriously impact the quality of life of the sufferer. The present study aimed to investigate the potential mechanisms underlying alterations in extracellular matrix (ECM) metabolism in the pathogenesis of POP, by investigating the expression of ECM components in human parametrial ligament fibroblasts (hPLFs) subject to various mechanical strain loads. Fibroblasts derived from parametrial ligaments were cultured from patients with POP and without malignant tumors, who underwent vaginal hysterectomy surgery. Fibroblasts at generations 3‑6 of exponential phase cells were selected, and a four‑point bending device was used for 0, 1,333 or 5,333 µ mechanical loading of cells at 0.5 Hz for 4 h. mRNA and protein expression levels of collagen type I α 1 chain (COL1A1), collagen type III α 1 chain (COL3A1), elastin, matrix metalloproteinase (MMP) ‑2 and ‑9, and transforming growth factor (TGF)‑β1 were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. Under increased mechanical strain (5,333 µ), mRNA and protein expression levels of COL1A1, COL3A1 elastin and TGF‑β1 decreased, particularly COL1A1; however, mRNA and protein expression levels of MMP‑2 and ‑9 were significantly increased, compared with the control group (0 µ strain). Following 1,333 µ mechanical strain, mRNA and protein expression levels of COL1A1, COL3A1 elastin and MMP‑2 increased, and MMP‑9 decreased, whereas no significant differences were observed in TGF‑β1 mRNA and protein expression levels. In conclusion, ECM alterations may be involved in pathogenesis of POP, with decreased synthesis and increased degradation of collagen and elastin. Furthermore, the TGF‑β1 signaling pathway may serve an important role in this process and thus may supply a new target and strategy for understanding the etiology and therapy of POP.
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Jie
J
Min
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Bingshu
B
Li
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Cheng
C
Liu
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Wenjun
W
Guo
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Shasha
S
Hong
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Jianming
J
Tang
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Li
L
Hong
D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008022:Ligaments / Q000166:cytology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000150:complications / Q000175:diagnosis; D056887:Pelvic Organ Prolapse / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D013314:Stress, Mechanical; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
C000716127:COL1A1 protein, human; C439971:COL3A1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; D053773:Transforming Growth Factor beta1; D004549:Elastin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9