Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
January-2017 Volume 15 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2017 Volume 15 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Excess mechanical stress and hydrogen peroxide remodel extracellular matrix of cultured human uterosacral ligament fibroblasts by disturbing the balance of MMPs/TIMPs via the regulation of TGF‑β1 signaling pathway

  • Authors:
    • Qifan Zhang
    • Cheng Liu
    • Shasha Hong
    • Jie Min
    • Qing Yang
    • Ming Hu
    • Yang Zhao
    • Li Hong
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
  • Pages: 423-430
    |
    Published online on: December 6, 2016
       https://doi.org/10.3892/mmr.2016.5994
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The regulation of the extracellular matrix (ECM) by mechanical stress is of interest as the ECM is essential in the development of pelvic organ prolapse. In the present study, the effect of overexposure to mechanical stress on the ECM, and the probable underlying mechanisms in cultured human uterosacral ligament fibroblasts (hUSLFs), was explored. Mechanical stress has an effect on oxidation‑antioxidation products in parametrial ligament fibroblasts. Thus, hUSLFs were incubated with different concentrations of hydrogen peroxide to elucidate any potential interactions. Excess mechanical stress and H2O2 inhibited cell proliferation, and decreased mRNA and protein expression levels of ECM components, collagen 1, collagen 3 and elastin. Further analysis revealed that the mRNA expression level of matrix metalloproteinase‑2 (MMP‑2) was increased and TIMP metallopeptidase inhibitor 2 (TIMP‑2) decreased, and in addition the MMP2/TIMP2 mRNA ratio was increased, which may facilitate the degradation of the ECM. Due to the key role of the transforming growth factor β1 (TGF‑β1)/mothers against decapentaplegic homolog 2 (Smad2) signaling pathway in fibrosis, the present study investigated the effect of excess mechanical stress and H2O2 on TGF‑β1/Smad2 signaling. The results indicated that excess mechanical stress and H2O2 treatment suppressed phosphorylated Smad2 expression and decreased the levels of TGF‑β1. Activation of the TGF‑β1 signaling pathway by either mechanical stress or H2O2 was demonstrated to attenuate cell proliferation and ECM components, and also increased the MMP2/TIMP2 mRNA ratio. These findings suggested that mechanical stress and H2O2 overexposure inhibit cell proliferation and remodel the ECM network via regulation of the TGF‑β1 signaling pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Pereira AM, Tudor C, Kanger JS, Subramaniam V and Martin-Blanco E: Integrin-dependent activation of the JNK signaling pathway by mechanical stress. PLoS One. 6:e261822011. View Article : Google Scholar : PubMed/NCBI

2 

Furumatsu T, Matsumoto E, Kanazawa T, Fujii M, Lu Z, Kajiki R and Ozaki T: Tensile strain increases expression of CCN2 and COL2A1 by activating TGF-β-Smad2/3 pathway in chondrocytic cells. J Biomech. 46:1508–1515. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Dieter AA, Wilkins MF and Wu JM: Epidemiological trends and future care needs for pelvic floor disorders. Curr Opin Obstet Gynecol. 27:380–384. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Majkusiak W, Horosz E, Tomasik P, Zwierzchowska A, Wielgoś M and Barcz E: Quality of life assessment in women after cervicosacropexy with polypropylene mesh for pelvic organ prolapse: A preliminary study. Prz Menopauzalny. 14:126–129. 2015.PubMed/NCBI

5 

Das J, Ghosh J, Manna P and Sil PC: Acetaminophen induced acute liver failure via oxidative stress and JNK activation: Protective role of taurine by the suppression of cytochrome P450 2E1. Free Radic Res. 44:340–355. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Ewies A and Elshafie M: High isoprostane level in cardinal ligament-derived fibroblasts and urine sample of women with uterine prolapse. BJOG. 116:126–128. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Li BS, Hong L, Min J, Wu DB, Hu M and Guo WJ: The expression of glutathione peroxidase-1 and the anabolism of collagen regulation pathway transforming growth factor-beta1-connective tissue growth factor in women with uterine prolapse and the clinic significance. Clin Exp Obstet Gynecol. 40:586–590. 2013.PubMed/NCBI

8 

Kamodyová N, Bañasová L, Janšáková K, Koborová I, Tóthová L, Stanko P and Celec P: Blood contamination in Saliva: Impact on the measurement of Salivary oxidative stress markers. Dis Markers. 2015:4792512015.PubMed/NCBI

9 

Bujak M and Frangogiannis NG: The role of TGF-beta signaling in myocardial infarction and cardiac remodeling. Cardiovasc Res. 74:184–195. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Huang XR, Chung AC, Yang F, Yue W, Deng C, Lau CP, Tse HF and Lan HY: Smad3 mediates cardiac inflammation and fibrosis in angiotensin II-induced hypertensive cardiac remodeling. Hypertension. 55:1165–1171. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Froese AR, Shimbori C, Bellaye PS, Inman M, Obex S, Fatima S, Jenkins G, Gauldie J, Ask K and Kolb M: Stretch-induced activation of transforming growth factor-β1 in pulmonary fibrosis. Am J Respir Crit Care Med. 194:84–96. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Wells RG: Fibrogenesis. V. TGF-beta signaling pathways. Am J Physiol Gastrointest Liver Physiol. 279:G845–G850. 2000.PubMed/NCBI

13 

Li FZ, Cai PC, Song LJ, Zhou LL, Zhang Q, Rao SS, Xia Y, Xiang F, Xin JB, Greer PA, et al: Crosstalk between calpain activation and TGF-β1 augments collagen-I synthesis in pulmonary fibrosis. Biochim Biophys Acta. 1852:1796–1804. 2015. View Article : Google Scholar : PubMed/NCBI

14 

De Landsheere L, Munaut C, Nusgens B, Maillard C, Rubod C, Nisolle M, Cosson M and Foidart JM: Histology of the vaginal wall in women with pelvic organ prolapse: A literature review. Int Urogynecol J. 24:2011–2020. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Chen B and Yeh J: Alterations in connective tissue metabolism in stress incontinence and prolapse. J Urol. 186:1768–1772. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C (T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

17 

Butt RP, Laurent GJ and Bishop JE: Mechanical load and polypeptide growth factors stimulate cardiac fibroblast activity. Ann N Y Acad Sci. 752:387–393. 1995. View Article : Google Scholar : PubMed/NCBI

18 

Kona S, Chellamuthu P, Xu H, Hills SR and Nguyen KT: Effects of cyclic strain and growth factors on vascular smooth muscle cell responses. Open Biomed Eng J. 3:28–38. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Yang G, Crawford RC and Wang JH: Proliferation and collagen production of human patellar tendon fibroblasts in response to cyclic uniaxial stretching in serum-free conditions. J Biomech. 37:1543–1550. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Kaneko D, Sasazaki Y, Kikuchi T, Ono T, Nemoto K, Matsumoto H and Toyama Y: Temporal effects of cyclic stretching on distribution and gene expression of integrin and cytoskeleton by ligament fibroblasts in vitro. Connect Tissue Res. 50:263–269. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Lu M, Gong X, Lu Y, Guo J, Wang C and Pan Y: Molecular cloning and functional characterization of a cell-permeable superoxide dismutase targeted to lung adenocarcinoma cells. Inhibition cell proliferation through the Akt/p27kip1 pathway. J Biol Chem. 281:13620–13627. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Niu Y, Xie T, Ge K, Lin Y and Lu S: Effects of extracellular matrix glycosylation on proliferation and apoptosis of human dermal fibroblasts via the receptor for advanced glycosylated end products. Am J Dermatopathol. 30:344–351. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Goh JT: Biomechanical and biochemical assessments for pelvic organ prolapse. Curr Opin Obstet Gynecol. 15:391–394. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Gressner AM and Weiskirchen R: Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets. J Cell Mol Med. 10:76–99. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Blavier L, Lazaryev A, Groffen J, Heisterkamp N, DeClerck YA and Kaartinen V: TGF-beta3-induced palatogenesis requires matrix metalloproteinases. Mol Biol Cell. 12:1457–1466. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Schilling TF, Nie Q and Lander AD: Dynamics and precision in retinoic acid morphogen gradients. Curr Opin Genet Dev. 22:562–569. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Verrecchia F, Chu ML and Mauviel A: Identification of novel TGF-beta/Smad gene targets in dermal fibroblasts using a combined cDNA microarray/promoter transactivation approach. J Biol Chem. 276:17058–17062. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Bai G, Yan G, Wang G, Wan P and Zhang R: Anti-hepatic fibrosis effects of a novel turtle shell decoction by inhibiting hepatic stellate cell proliferation and blocking TGF-β1/Smad signaling pathway in rats. Oncol Rep. 36:2902–2910. 2016.PubMed/NCBI

29 

Moustakas A and Heldin CH: Non-Smad TGF-beta signals. J Cell Sci. 118:3573–3584. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Trager N, Smith A, Iv G Wallace, Azuma M, Inoue J, Beeson C, Haque A and Banik NL: Effects of a novel orally administered calpain inhibitor SNJ-1945 on immunomodulation and neurodegeneration in a murine model of multiple sclerosis. J Neurochem. 130:268–279. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Secker GA, Shortt AJ, Sampson E, Schwarz QP, Schultz GS and Daniels JT: TGFbeta stimulated re-epithelialisation is regulated by CTGF and Ras/MEK/ERK signalling. Exp Cell Res. 314:131–142. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Xi L, Xiao C, Bandsma RH, Naples M, Adeli K and Lewis GF: C-reactive protein impairs hepatic insulin sensitivity and insulin signaling in rats: Role of mitogen-activated protein kinases. Hepatology. 53:127–135. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang Q, Liu C, Hong S, Min J, Yang Q, Hu M, Zhao Y and Hong L: Excess mechanical stress and hydrogen peroxide remodel extracellular matrix of cultured human uterosacral ligament fibroblasts by disturbing the balance of MMPs/TIMPs via the regulation of TGF‑β1 signaling pathway. Mol Med Rep 15: 423-430, 2017.
APA
Zhang, Q., Liu, C., Hong, S., Min, J., Yang, Q., Hu, M. ... Hong, L. (2017). Excess mechanical stress and hydrogen peroxide remodel extracellular matrix of cultured human uterosacral ligament fibroblasts by disturbing the balance of MMPs/TIMPs via the regulation of TGF‑β1 signaling pathway. Molecular Medicine Reports, 15, 423-430. https://doi.org/10.3892/mmr.2016.5994
MLA
Zhang, Q., Liu, C., Hong, S., Min, J., Yang, Q., Hu, M., Zhao, Y., Hong, L."Excess mechanical stress and hydrogen peroxide remodel extracellular matrix of cultured human uterosacral ligament fibroblasts by disturbing the balance of MMPs/TIMPs via the regulation of TGF‑β1 signaling pathway". Molecular Medicine Reports 15.1 (2017): 423-430.
Chicago
Zhang, Q., Liu, C., Hong, S., Min, J., Yang, Q., Hu, M., Zhao, Y., Hong, L."Excess mechanical stress and hydrogen peroxide remodel extracellular matrix of cultured human uterosacral ligament fibroblasts by disturbing the balance of MMPs/TIMPs via the regulation of TGF‑β1 signaling pathway". Molecular Medicine Reports 15, no. 1 (2017): 423-430. https://doi.org/10.3892/mmr.2016.5994
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Q, Liu C, Hong S, Min J, Yang Q, Hu M, Zhao Y and Hong L: Excess mechanical stress and hydrogen peroxide remodel extracellular matrix of cultured human uterosacral ligament fibroblasts by disturbing the balance of MMPs/TIMPs via the regulation of TGF‑β1 signaling pathway. Mol Med Rep 15: 423-430, 2017.
APA
Zhang, Q., Liu, C., Hong, S., Min, J., Yang, Q., Hu, M. ... Hong, L. (2017). Excess mechanical stress and hydrogen peroxide remodel extracellular matrix of cultured human uterosacral ligament fibroblasts by disturbing the balance of MMPs/TIMPs via the regulation of TGF‑β1 signaling pathway. Molecular Medicine Reports, 15, 423-430. https://doi.org/10.3892/mmr.2016.5994
MLA
Zhang, Q., Liu, C., Hong, S., Min, J., Yang, Q., Hu, M., Zhao, Y., Hong, L."Excess mechanical stress and hydrogen peroxide remodel extracellular matrix of cultured human uterosacral ligament fibroblasts by disturbing the balance of MMPs/TIMPs via the regulation of TGF‑β1 signaling pathway". Molecular Medicine Reports 15.1 (2017): 423-430.
Chicago
Zhang, Q., Liu, C., Hong, S., Min, J., Yang, Q., Hu, M., Zhao, Y., Hong, L."Excess mechanical stress and hydrogen peroxide remodel extracellular matrix of cultured human uterosacral ligament fibroblasts by disturbing the balance of MMPs/TIMPs via the regulation of TGF‑β1 signaling pathway". Molecular Medicine Reports 15, no. 1 (2017): 423-430. https://doi.org/10.3892/mmr.2016.5994
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team