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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
December-2017 Volume 14 Issue 6

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
December-2017 Volume 14 Issue 6

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

Kaempferol targets estrogen‑related receptor α and suppresses the angiogenesis of human retinal endothelial cells under high glucose conditions

  • Authors:
    • Yan Wu
    • Qinmei Zhang
    • Rui Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, The Second Clinical College of Jinan University, Shenzhen Peoples' Hospital, Shenzhen, Guangdong 518020, P.R. China
  • Pages: 5576-5582
    |
    Published online on: October 3, 2017
       https://doi.org/10.3892/etm.2017.5261
  • 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

Diabetic retinopathy (DR) is the most common complication of diabetes and a major cause of new‑onset blindness in the developed world. The present study aimed to examine the effect of kaempferol on high glucose‑induced human retinal endothelial cells (HRECs) in vitro. The expression levels of various mRNAs and proteins were measured by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting, respectively. The target of kaempferol was determined using a luciferase reporter assay. In addition, HREC proliferation, migration and cell sprouting were determined using Cell Counting kit‑8, wound scratch and tube formation assays, respectively. RT‑qPCR and western blotting results showed that treatment with 30 mM glucose for 12, 24 and 48 h increased the expression level of estrogen‑related receptor α (ERRα) mRNA and protein. The luciferase reporter assay demonstrated that kaempferol inhibited ERRα activity in HRECs. Compared with 5 mM normal glucose treatment, high (30 mM) glucose significantly promoted the proliferation, migration and tube formation of HRECs, which was antagonized by 10 and 30 µM kaempferol in a dose‑dependent manner. Treatment with 30 mM glucose also increased the expression of vascular endothelial growth factor (VEGF) mRNA and protein, and the expression levels of VEGF mRNA and protein were suppressed by kaempferol (10 and 30 µM). Kaempferol (30 µM) treatment also increased the expression levels of thrombospondin 1 (TSP‑1) and a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS‑1) mRNA; however, TSP‑1 and ADAMTS‑1 levels did not differ between high glucose and normal (5 mM) glucose conditions. The results of this study suggest that kaempferol targets ERRα and suppresses the angiogenesis of HRECs under high glucose conditions. Kaempferol may be a potential drug for use in controlling the progression of DR; however, in vivo studies are required to evaluate its efficacy and safety.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Yu DY, Cringle SJ, Su EN, Yu PK, Jerums G and Cooper ME: Pathogenesis and intervention strategies in diabetic retinopathy. Clin Exp Ophthalmol. 29:164–166. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Hendrick AM, Gibson MV and Kulshreshtha A: Diabetic Retinopathy. Prim Care. 42:451–464. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Wan TT, Li XF, Sun YM, Li YB and Su Y: Recent advances in understanding the biochemical and molecular mechanism of diabetic retinopathy. Biomed Pharmacother. 74:145–147. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Osaadon P, Fagan XJ, Lifshitz T and Levy J: A review of anti-VEGF agents for proliferative diabetic retinopathy. Eye (Lond). 28:510–520. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Yoo SY and Kwon SM: Angiogenesis and its therapeutic opportunities. Mediators Inflamm. 2013:1271702013. View Article : Google Scholar : PubMed/NCBI

6 

Distler JH, Hirth A, Kurowska-Stolarska M, Gay RE, Gay S and Distler O: Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med. 47:149–161. 2003.PubMed/NCBI

7 

Sorenson CM, Wang S, Gendron R, Paradis H and Sheibani N: Thrombospondin-1 deficiency exacerbates the pathogenesis of diabetic retinopathy. J Diabetes Metab. Suppl 12:2013.PubMed/NCBI

8 

Basile DP, Fredrich K, Chelladurai B, Leonard EC and Parrish AR: Renal ischemia reperfusion inhibits VEGF expression and induces ADAMTS-1, a novel VEGF inhibitor. Am J Physiol Renal Physiol. 294:F928–F936. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Ranhotra HS: The estrogen-related receptor alpha: The oldest, yet an energetic orphan with robust biological functions. J Recept Signal Transduct Res. 30:193–205. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Zhang K, Lu J, Mori T, Smith-Powell L, Synold TW, Chen S and Wen W: Baicalin increases VEGF expression and angiogenesis by activating the ERR{alpha}/PGC-1{alpha} pathway. Cardiovasc Res. 89:426–435. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Olszewska MA: New validated high-performance liquid chromatographic method for simultaneous analysis of ten flavonoid aglycones in plant extracts using a C18 fused-core column and acetonitrile-tetrahydrofuran gradient. J Sep Sci. 35:2174–2183. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Chen AY and Chen YC: A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention. Food Chem. 138:2099–2107. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Kim SH and Choi KC: Anti-cancer effect and underlying mechanism (s) of kaempferol, a phytoestrogen, on the regulation of apoptosis in diverse cancer cell models. Toxicol Res. 29:229–234. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Wang J, Fang F, Huang Z, Wang Y and Wong C: Kaempferol is an estrogen-related receptor alpha and gamma inverse agonist. FEBS Lett. 583:643–647. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Luo H, Rankin GO, Juliano N, Jiang BH and Chen YC: Kaempferol inhibits VEGF expression and in vitro angiogenesis through a novel ERK-NFκB-cMyc-p21 pathway. Food Chem. 130:321–328. 2012. 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 

Dagher Z, Park YS, Asnaghi V, Hoehn T, Gerhardinger C and Lorenzi M: Studies of rat and human retinas predict a role for the polyol pathway in human diabetic retinopathy. Diabetes. 53:2404–2411. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Yuan L, Hu J, Luo Y, Liu Q, Li T, Parish CR, Freeman C, Zhu X, Ma W, Hu X, et al: Upregulation of heparanase in high-glucose-treated endothelial cells promotes endothelial cell migration and proliferation and correlates with Akt and extracellular-signal-regulated kinase phosphorylation. Mol Vis. 18:1684–1695. 2012.PubMed/NCBI

19 

Chen X, Li J, Li M, Zeng M, Li T, Xiao W, Li J, Wu Q, Ke X, Luo D, et al: KH902 suppresses high glucose-induced migration and sprouting of human retinal endothelial cells by blocking VEGF and PIGF. Diabetes Obes Metab. 15:224–233. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Chen Z, Liu G, Xiao Y and Lu P: Adrenomedullin22-52 suppresses high-glucose-induced migration, proliferation, and tube formation of human retinal endothelial cells. Mol Vis. 20:259–269. 2014.PubMed/NCBI

21 

Hayashi JN, Ito H, Kanayasu T, Asuwa N, Morita I, Ishii T and Murota S: Effects of glucose on migration, proliferation and tube formation by vascular endothelial cells. Virchows Arch B Cell Pathol Incl Mol Pathol. 60:245–252. 1991. View Article : Google Scholar : PubMed/NCBI

22 

Premanand C, Rema M, Sameer MZ, Sujatha M and Balasubramanyam M: Effect of curcumin on proliferation of human retinal endothelial cells under in vitro conditions. Invest Ophthalmol Vis Sci. 47:2179–2184. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Zou C, Yu S, Xu Z, Wu D, Ng CF, Yao X, Yew DT, Vanacker JM and Chan FL: ERRalpha augments HIF-1 signalling by directly interacting with HIF-1α in normoxic and hypoxic prostate cancer cells. J Pathol. 233:61–73. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Arany Z, Foo SY, Ma Y, Ruas JL, Bommi-Reddy A, Girnun G, Cooper M, Laznik D, Chinsomboon J, Rangwala SM, et al: HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature. 451:1008–1012. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Cao D, Zhou H, Zhao J, Jin L, Yu W, Yan H, Hu Y and Guo T: PGC-1α integrates glucose metabolism and angiogenesis in multiple myeloma cells by regulating VEGF and GLUT-4. Oncol Rep. 31:1205–1210. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Liang F, Han Y, Gao H, Xin S, Chen S, Wang N, Qin W, Zhong H, Lin S, Yao X and Li S: Kaempferol identified by zebrafish assay and fine fractionations strategy from dysosma versipellis inhibits angiogenesis through VEGF and FGF pathways. Sci Rep. 5:144682015. View Article : Google Scholar : PubMed/NCBI

27 

Betts-Obregon BS, Vellanki S, Buikema J, Tsin AT and Wright K: Effect of glucose on retinal endothelial cell viability and VEGF secretion. HSOA J Cell Biol Cell Metabol. 3:pii: 008. 2016.PubMed/NCBI

28 

DiPietro LA, Nebgen DR and Polverini PJ: Downregulation of endothelial cell thrombospondin 1 enhances in vitro angiogenesis. J Vasc Res. 31:178–185. 1994. View Article : Google Scholar : PubMed/NCBI

29 

Sun Y, Huang J and Yang Z: The roles of ADAMTS in angiogenesis and cancer. Tumour Biol. 36:4039–4051. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Lee NV, Sato M, Annis DS, Loo JA, Wu L, Mosher DF and Iruela-Arispe ML: ADAMTS1 mediates the release of antiangiogenic polypeptides from TSP1 and 2. EMBO J. 25:5270–5283. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Krampert M, Kuenzle S, Thai SN, Lee N, Iruela-Arispe ML and Werner S: ADAMTS1 proteinase is up-regulated in wounded skin and regulates migration of fibroblasts and endothelial cells. J Biol Chem. 280:23844–23852. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wu Y, Zhang Q and Zhang R: Kaempferol targets estrogen‑related receptor α and suppresses the angiogenesis of human retinal endothelial cells under high glucose conditions. Exp Ther Med 14: 5576-5582, 2017.
APA
Wu, Y., Zhang, Q., & Zhang, R. (2017). Kaempferol targets estrogen‑related receptor α and suppresses the angiogenesis of human retinal endothelial cells under high glucose conditions. Experimental and Therapeutic Medicine, 14, 5576-5582. https://doi.org/10.3892/etm.2017.5261
MLA
Wu, Y., Zhang, Q., Zhang, R."Kaempferol targets estrogen‑related receptor α and suppresses the angiogenesis of human retinal endothelial cells under high glucose conditions". Experimental and Therapeutic Medicine 14.6 (2017): 5576-5582.
Chicago
Wu, Y., Zhang, Q., Zhang, R."Kaempferol targets estrogen‑related receptor α and suppresses the angiogenesis of human retinal endothelial cells under high glucose conditions". Experimental and Therapeutic Medicine 14, no. 6 (2017): 5576-5582. https://doi.org/10.3892/etm.2017.5261
Copy and paste a formatted citation
x
Spandidos Publications style
Wu Y, Zhang Q and Zhang R: Kaempferol targets estrogen‑related receptor α and suppresses the angiogenesis of human retinal endothelial cells under high glucose conditions. Exp Ther Med 14: 5576-5582, 2017.
APA
Wu, Y., Zhang, Q., & Zhang, R. (2017). Kaempferol targets estrogen‑related receptor α and suppresses the angiogenesis of human retinal endothelial cells under high glucose conditions. Experimental and Therapeutic Medicine, 14, 5576-5582. https://doi.org/10.3892/etm.2017.5261
MLA
Wu, Y., Zhang, Q., Zhang, R."Kaempferol targets estrogen‑related receptor α and suppresses the angiogenesis of human retinal endothelial cells under high glucose conditions". Experimental and Therapeutic Medicine 14.6 (2017): 5576-5582.
Chicago
Wu, Y., Zhang, Q., Zhang, R."Kaempferol targets estrogen‑related receptor α and suppresses the angiogenesis of human retinal endothelial cells under high glucose conditions". Experimental and Therapeutic Medicine 14, no. 6 (2017): 5576-5582. https://doi.org/10.3892/etm.2017.5261
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