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
May-2018 Volume 17 Issue 5

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
May-2018 Volume 17 Issue 5

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

Role of SGLT1 in high glucose level-induced MMP-2 expression in human cardiac fibroblasts

  • Authors:
    • Liping Meng
    • Hiroyasu Uzui
    • Hangyuan Guo
    • Hiroshi Tada
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910‑1193, Japan, Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang 312000, P.R. China
  • Pages: 6887-6892
    |
    Published online on: March 6, 2018
       https://doi.org/10.3892/mmr.2018.8688
  • 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

Cardiac fibrosis is a major pathological manifestation of diabetic cardiomyopathy (DCM), which leads to cardiac remodeling, dilated cardiomyopathy and congestive heart failure. Human cardiac fibroblasts (HCF) constitute the predominant cell type in the heart and matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are also involved in cardiac fibrosis. However, it is unclear whether high glucose levels affect the expression of MMPs and TIMPs in HCF. Sodium‑glucose cotransporter (SGLT) inhibitors have been developed as therapeutic agents and the anti‑DCM effect of SGLT inhibitors has been demonstrated by previous studies. However, whether SLGT inhibitors protect the diabetic heart by directly inhibiting the SGLTs in HCF in addition to lowering the blood glucose levels, has not yet been determined. In the present study, increased MMP‑2 expression was noted in HCFs in response to high glucose levels, which may be reversed by phlorizin (inhibits both SGLT1 and SGLT2), but not dapagliflozin (inhibits SGLT2). In addition, SGLT1 was revealed to be present in the HCFs and high glucose level was demonstrated to increase SGLT1 expression, which may be attenuated by phlorizin. Therefore it was concluded that high glucose levels induced MMP‑2 expression in the HCFs, potentially by upregulating SGLT1. SGLT1 inhibition may be a novel strategy for the treatment of DCM.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Fang ZY, Prins JB and Marwick TH: Diabetic cardiomyopathy: Evidence, mechanisms and therapeutic implications. Endocr Rev. 25:543–567. 2004. View Article : Google Scholar : PubMed/NCBI

2 

DeCoux A, Lindsey ML, Villarreal F, Garcia RA and Schulz R: Myocardial matrix metalloproteinase-2: Inside out and upside down. J Mol Cell Cardiol. 77:64–72. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Li Q, Sun SZ, Wang Y, Tian YJ and Liu MH: The roles of MMP-2/TIMP-2 in extracellular matrix remodelling in the hearts of STZ-induced diabetic rats. Acta Cardiol. 62:485–491. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Chen SL, Hu ZY, Zuo GF, Li MH and Li B: I(f) current channel inhibitor (ivabradine) deserves cardioprotective effect via down-regulating the expression of matrix metalloproteinase (MMP)-2 and attenuating apoptosis in diabetic mice. BMC Cardiovasc Disord. 14:1502014. View Article : Google Scholar : PubMed/NCBI

5 

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, et al: Empagliflozin, cardiovascular outcomes and mortality in type 2 diabetes. N Engl J Med. 373:2117–2128. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Cefalu WT, Leiter LA, de Bruin TW, Gause-Nilsson I, Sugg J and Parikh SJ: Dapagliflozin's effects on glycemia and cardiovascular risk factors in high-risk patients with type 2 diabetes: A 24-week, multicenter, randomized, double-blind, placebo-controlled study with a 28-week extension. Diabetes Care. 38:1218–1227. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Song P, Onishi A, Koepsell H and Vallon V: Sodium glucose cotransporter SGLT1 as a therapeutic target in diabetes mellitus. Exp Opin Ther Targets. 20:1109–1125. 2016. View Article : Google Scholar

8 

Kashiwagi Y, Nagoshi T, Yoshino T, Tanaka TD, Ito K, Harada T, Takahashi H, Ikegami M, Anzawa R and Yoshimura M: Expression of SGLT1 in human hearts and impairment of cardiac glucose uptake by phlorizin during ischemia-reperfusion injury in mice. PLoS One. 10:e01306052015. View Article : Google Scholar : PubMed/NCBI

9 

Banerjee SK, Ramani R, Saba S, Rager J, Tian R, Mathier MA and Ahmad F: A PRKAG2 mutation causes biphasic changes in myocardial AMPK activity and does not protect against ischemia. Biochem Biophys Res Commun. 360:381–387. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Ramratnam M, Sharma RK, D'Auria S, Lee SJ, Wang D, Huang XY and Ahmad F: Transgenic knockdown of cardiac sodium/glucose cotransporter 1 (SGLT1) attenuates PRKAG2 cardiomyopathy, whereas transgenic overexpression of cardiac SGLT1 causes pathologic hypertrophy and dysfunction in mice. J Am Heart Assoc. 3:e0008992014. View Article : Google Scholar : PubMed/NCBI

11 

Das S, Mandal M, Chakraborti T, Mandal A and Chakraborti S: Isolation of MMP-2 from MMP-2/TIMP-2 complex: Characterization of the complex and the free enzyme in pulmonary vascular smooth muscle plasma membrane. Biochim Biophys Acta. 1674:158–174. 2004.PubMed/NCBI

12 

Avolio C, Filippi M, Tortorella C, Rocca MA, Ruggieri M, Agosta F, Tomassini V, Pozzilli C, Stecchi S, Giaquinto P, et al: Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: Relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment. Mult Scler. 11:441–446. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Liu X, Song X, Lu J, Chen X, Liang E, Liu X, Zhang M, Zhang Y, Du Z and Zhao Y: Neferine inhibits proliferation and collagen synthesis induced by high glucose in cardiac fibroblasts and reduces cardiac fibrosis in diabetic mice. Oncotarget. 7:61703–61715. 2016.PubMed/NCBI

14 

Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW and Grishman A: New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 30:595–602. 1972. View Article : Google Scholar : PubMed/NCBI

15 

Jia G, Whaley-Connell A and Sowers JR: Diabetic cardiomyopathy: A hyperglycaemia- and insulin-resistance-induced heart disease. Diabetologia. 61:21–28. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Zou C, Liu X, Xie R, Bao Y, Jin Q, Jia X, Li L and Liu R: Deferiprone attenuates inflammation and myocardial fibrosis in diabetic cardiomyopathy rats. Biochem Biophys Res Commun. 486:930–936. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Lo SH, Hsu CT, Niu HS, Niu CS, Cheng JT and Chen ZC: Cryptotanshinone inhibits STAT3 signaling to alleviate cardiac fibrosis in type 1-like diabetic rats. Phytother Res. 31:638–646. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Wang XW, Zhang FX, Yang F, Ding ZF, Agarwal N, Guo ZK and Mehta JL: Effects of linagliptin and liraglutide on glucose- and angiotensin II-induced collagen formation and cytoskeleton degradation in cardiac fibroblasts in vitro. Acta Pharmacol Sin. 37:1349–1358. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Li J, Dai Y, Su Z and Wei G: MicroRNA-9 inhibits high glucose-induced proliferation, differentiation and collagen accumulation of cardiac fibroblasts by down-regulation of TGFBR2. Biosci Rep. 36:e004172016. View Article : Google Scholar : PubMed/NCBI

20 

Meng L, Liu L, Zhou C, Pan S, Zhai X, Jiang C, Guo Y, Ji Z, Chi J, Peng F and Guo H: Polyphenols and polypeptides in chinese rice wine inhibit homocysteine-induced proliferation and migration of vascular smooth muscle cells. J Cardiovasc Pharmacol. 67:482–490. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Shi YF, Chi JF, Tang WL, Xu FK, Liu LB, Ji Z, Lv HT and Guo HY: Effects of rosuvastatin on the production and activation of matrix metalloproteinase-2 and migration of cultured rat vascular smooth muscle cells induced by homocysteine. J Zhejiang Univ Sci B. 14:696–704. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Siddesha JM, Valente AJ, Sakamuri SS, Yoshida T, Gardner JD, Somanna N, Takahashi C, Noda M and Chandrasekar B: Angiotensin II stimulates cardiac fibroblast migration via the differential regulation of matrixins and RECK. J Mol Cell Cardiol. 65:9–18. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Cauwe B and Opdenakker G: Intracellular substrate cleavage: A novel dimension in the biochemistry, biology and pathology of matrix metalloproteinases. Crit Rev Biochem Mol Biol. 45:351–423. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Hughes BG, Fan X, Cho WJ and Schulz R: MMP-2 is localized to the mitochondria-associated membrane of the heart. Am J Physiol Heart Circ Physiol. 306:H764–H770. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Westermann D, Savvatis K, Lindner D, Zietsch C, Becher PM, Hammer E, Heimesaat MM, Bereswill S, Volker U, Escher F, et al: Reduced degradation of the chemokine MCP-3 by matrix metalloproteinase-2 exacerbates myocardial inflammation in experimental viral cardiomyopathy. Circulation. 124:2082–2093. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Chen J, Williams S, Ho S, Loraine H, Hagan D, Whaley JM and Feder JN: Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members. Diabetes Ther. 1:57–92. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Jin X, Yi L, Chen ML, Chen CY, Chang H, Zhang T, Wang L, Zhu JD, Zhang QY and Mi MT: Delphinidin-3-glucoside protects against oxidized low-density lipoprotein-induced mitochondrial dysfunction in vascular endothelial cells via the sodium-dependent glucose transporter SGLT1. PLoS One. 8:e686172013. View Article : Google Scholar : PubMed/NCBI

28 

Balteau M, Tajeddine N, de Meester C, Ginion A, Des Rosiers C, Brady NR, Sommereyns C, Horman S, Vanoverschelde JL, Gailly P, et al: NADPH oxidase activation by hyperglycaemia in cardiomyocytes is independent of glucose metabolism but requires SGLT1. Cardiovasc Res. 92:237–246. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Van Steenbergen A, Balteau M, Ginion A, Ferte L, Battault S, Ravenstein CM, Balligand JL, Daskalopoulos EP, Gilon P, Despa F, et al: Sodium-myoinositol cotransporter-1, SMIT1, mediates the production of reactive oxygen species induced by hyperglycemia in the heart. Sci Rep. 7:411662017. View Article : Google Scholar : PubMed/NCBI

30 

Di Franco A, Cantini G, Tani A, Coppini R, Zecchi-Orlandini S, Raimondi L, Luconi M and Mannucci E: Sodium-dependent glucose transporters (SGLT) in human ischemic heart: A new potential pharmacological target. Int J Cardiol. 243:86–90. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Ye Y, Bajaj M, Yang HC, Perez-Polo JR and Birnbaum Y: SGLT-2 inhibition with dapagliflozin reduces the activation of the Nlrp3/ASC inflammasome and attenuates the development of diabetic cardiomyopathy in mice with type 2 diabetes. Further augmentation of the effects with saxagliptin, a DPP4 inhibitor. Cardiovasc Drugs Ther. 31:119–132. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Joubert M, Jagu B, Montaigne D, Marechal X, Tesse A, Ayer A, Dollet L, Le May C, Toumaniantz G, Manrique A, et al: The sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents cardiomyopathy in a diabetic lipodystrophic mouse model. Diabetes. 66:1030–1040. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Meng L, Uzui H, Guo H and Tada H: Role of SGLT1 in high glucose level-induced MMP-2 expression in human cardiac fibroblasts. Mol Med Rep 17: 6887-6892, 2018.
APA
Meng, L., Uzui, H., Guo, H., & Tada, H. (2018). Role of SGLT1 in high glucose level-induced MMP-2 expression in human cardiac fibroblasts. Molecular Medicine Reports, 17, 6887-6892. https://doi.org/10.3892/mmr.2018.8688
MLA
Meng, L., Uzui, H., Guo, H., Tada, H."Role of SGLT1 in high glucose level-induced MMP-2 expression in human cardiac fibroblasts". Molecular Medicine Reports 17.5 (2018): 6887-6892.
Chicago
Meng, L., Uzui, H., Guo, H., Tada, H."Role of SGLT1 in high glucose level-induced MMP-2 expression in human cardiac fibroblasts". Molecular Medicine Reports 17, no. 5 (2018): 6887-6892. https://doi.org/10.3892/mmr.2018.8688
Copy and paste a formatted citation
x
Spandidos Publications style
Meng L, Uzui H, Guo H and Tada H: Role of SGLT1 in high glucose level-induced MMP-2 expression in human cardiac fibroblasts. Mol Med Rep 17: 6887-6892, 2018.
APA
Meng, L., Uzui, H., Guo, H., & Tada, H. (2018). Role of SGLT1 in high glucose level-induced MMP-2 expression in human cardiac fibroblasts. Molecular Medicine Reports, 17, 6887-6892. https://doi.org/10.3892/mmr.2018.8688
MLA
Meng, L., Uzui, H., Guo, H., Tada, H."Role of SGLT1 in high glucose level-induced MMP-2 expression in human cardiac fibroblasts". Molecular Medicine Reports 17.5 (2018): 6887-6892.
Chicago
Meng, L., Uzui, H., Guo, H., Tada, H."Role of SGLT1 in high glucose level-induced MMP-2 expression in human cardiac fibroblasts". Molecular Medicine Reports 17, no. 5 (2018): 6887-6892. https://doi.org/10.3892/mmr.2018.8688
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