Butyrate Increases the Formation of Anti-angiogenic Vascular Endothelial Growth Factor Variants in Human Lung Microvascular Endothelial Cells

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2010 Mar 10

PMID 20213511

Citations 8

Authors

J Ciura

P P Jagodzinski

Affiliations

Soon will be listed here.

Abstract

The primary transcript of vascular endothelial growth factor (VEGF) can be alternatively spliced and translated to pro-angiogenic and anti-angiogenic VEGF variants. We investigated the effect of sodium butyrate (NaB) on pro-angiogenic and anti-angiogenic VEGF variants production in immortalized human lung microvascular endothelial cells (HLMEC). These cells were cultured in the absence or in the presence of NaB, followed by total RNA and protein isolation. The transcript and protein levels of pro-angiogenic and anti-angiogenic VEGF variants were evaluated by reverse transcription, real-time quantitative PCR and western blot analysis. We found that NaB significantly increased the anti-angiogenic transcript and protein levels of the VEGF 121b, VEGF165b and VEGF189b variants in HLMEC cells. We did not find the pro-angiogenic VEGF189a transcript variant either in control or NaB treated cells. By contrast, the pro-angiogenic VEGF121a and VEGF165a transcript variants were present in HLMEC cells, but their levels were slightly modulated in the cells treated with NaB compared to controls. Since anti-angiogenic VEGF variants inhibit angiogenesis and tumour progression, and NaB is considered an anticancer drug, our findings may have clinical significance.

Citing Articles

Glucoregulatory effect of butyrate is associated with elevated circulating VEGF and reduced cardiac lactate in high fructose fed rats.

Oyabambi A, Bamidele O, Boluwatife A, Adedayo L Heliyon. 2023; 9(11):e22008.

PMID: 38034766 PMC: 10682615. DOI: 10.1016/j.heliyon.2023.e22008.

Role of Butyrate, a Gut Microbiota Derived Metabolite, in Cardiovascular Diseases: A comprehensive narrative review.

Amiri P, Hosseini S, Ghaffari S, Tutunchi H, Ghaffari S, Mosharkesh E Front Pharmacol. 2022; 12:837509.

PMID: 35185553 PMC: 8847574. DOI: 10.3389/fphar.2021.837509.

Trimetazidine ameliorates hindlimb ischaemic damage in type 2 diabetic mice.

Yang Y, Xu Q, Li T, Shao S Ann Med. 2021; 53(1):1099-1107.

PMID: 34259103 PMC: 8281072. DOI: 10.1080/07853890.2021.1925147.

The effect of butyric acid with autogenous omental graft on healing of experimental Achilles tendon injury in rabbits.

Jahani S, Moslemi H, Dehghan M, Sedaghat R, Mazaheri Nezhad R, Rezaee Moghaddam D Iran J Vet Res. 2016; 16(1):100-4.

PMID: 27175160 PMC: 4789249.

Alternative splicing regulated by butyrate in bovine epithelial cells.

Wu S, Li C, Huang W, Li W, Li R PLoS One. 2012; 7(6):e39182.

PMID: 22720068 PMC: 3375255. DOI: 10.1371/journal.pone.0039182.

References

Gozzini A, Rovida E, Dello Sbarba P, Galimberti S, Santini V, Galimbert S . Butyrates, as a single drug, induce histone acetylation and granulocytic maturation: possible selectivity on core binding factor-acute myeloid leukemia blasts. Cancer Res. 2003; 63(24):8955-61. View

Onen I, Konac E, Eroglu M, Guneri C, Biri H, Ekmekci A . No association between polymorphism in the vascular endothelial growth factor gene at position -460 and sporadic prostate cancer in the Turkish population. Mol Biol Rep. 2007; 35(1):17-22. DOI: 10.1007/s11033-006-9046-2. View

Nissim-Rafinia M, Aviram M, Randell S, Shushi L, Ozeri E, Chiba-Falek O . Restoration of the cystic fibrosis transmembrane conductance regulator function by splicing modulation. EMBO Rep. 2004; 5(11):1071-7. PMC: 1299168. DOI: 10.1038/sj.embor.7400273. View

Ogawa H, Rafiee P, Fisher P, Johnson N, Otterson M, Binion D . Sodium butyrate inhibits angiogenesis of human intestinal microvascular endothelial cells through COX-2 inhibition. FEBS Lett. 2003; 554(1-2):88-94. DOI: 10.1016/s0014-5793(03)01110-4. View

Miller-Kasprzak E, Jagodzinski P . Endothelial progenitor cells as a new agent contributing to vascular repair. Arch Immunol Ther Exp (Warsz). 2007; 55(4):247-59. DOI: 10.1007/s00005-007-0027-5. View

Scharlau D, Borowicki A, Habermann N, Hofmann T, Klenow S, Miene C . Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutat Res. 2009; 682(1):39-53. DOI: 10.1016/j.mrrev.2009.04.001. View

Woolard J, Wang W, Bevan H, Qiu Y, Morbidelli L, Pritchard-Jones R . VEGF165b, an inhibitory vascular endothelial growth factor splice variant: mechanism of action, in vivo effect on angiogenesis and endogenous protein expression. Cancer Res. 2004; 64(21):7822-35. DOI: 10.1158/0008-5472.CAN-04-0934. View

Piotrowska H, Jagodzinski P . Trichostatin A, sodium butyrate, and 5-aza-2'-deoxycytidine alter the expression of glucocorticoid receptor alpha and beta isoforms in Hut-78 T- and Raji B-lymphoma cell lines. Biomed Pharmacother. 2007; 61(7):451-4. DOI: 10.1016/j.biopha.2007.03.007. View

Park J, Cho C, Ramachandran S, Shin S, Kwon S, Kwon S . Augmentation of sodium butyrate-induced apoptosis by phosphatidylinositol 3-kinase inhibition in the human cervical cancer cell-line. Cancer Res Treat. 2009; 38(2):112-7. PMC: 2741669. DOI: 10.4143/crt.2006.38.2.112. View

10.

Folkman J . Angiogenesis and apoptosis. Semin Cancer Biol. 2003; 13(2):159-67. DOI: 10.1016/s1044-579x(02)00133-5. View

11.

Hicklin D, Ellis L . Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2004; 23(5):1011-27. DOI: 10.1200/JCO.2005.06.081. View

12.

Pellizzaro C, Coradini D, Daidone M . Modulation of angiogenesis-related proteins synthesis by sodium butyrate in colon cancer cell line HT29. Carcinogenesis. 2002; 23(5):735-40. DOI: 10.1093/carcin/23.5.735. View

13.

Rennel E, Waine E, Guan H, Schuler Y, Leenders W, Woolard J . The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice. Br J Cancer. 2008; 98(7):1250-7. PMC: 2359649. DOI: 10.1038/sj.bjc.6604309. View

14.

Diaz R, Pena C, Silva J, Lorenzo Y, Garcia V, Garcia J . p73 Isoforms affect VEGF, VEGF165b and PEDF expression in human colorectal tumors: VEGF165b downregulation as a marker of poor prognosis. Int J Cancer. 2008; 123(5):1060-7. DOI: 10.1002/ijc.23619. View

15.

Byrne A, Bouchier-Hayes D, Harmey J . Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). J Cell Mol Med. 2005; 9(4):777-94. PMC: 6740098. DOI: 10.1111/j.1582-4934.2005.tb00379.x. View

16.

Lu Q, Yang Y, Chen C, Davis M, Byrd J, Etherton M . Zn2+-chelating motif-tethered short-chain fatty acids as a novel class of histone deacetylase inhibitors. J Med Chem. 2004; 47(2):467-74. DOI: 10.1021/jm0303655. View

17.

Choi Y . Apoptosis of U937 human leukemic cells by sodium butyrate is associated with inhibition of telomerase activity. Int J Oncol. 2006; 29(5):1207-13. View

18.

Miller-Kasprzak E, Jagodzinski P . 5-Aza-2'-deoxycytidine increases the expression of anti-angiogenic vascular endothelial growth factor 189b variant in human lung microvascular endothelial cells. Biomed Pharmacother. 2007; 62(3):158-63. DOI: 10.1016/j.biopha.2007.07.015. View

19.

Zgouras D, Wachtershauser A, Frings D, Stein J . Butyrate impairs intestinal tumor cell-induced angiogenesis by inhibiting HIF-1alpha nuclear translocation. Biochem Biophys Res Commun. 2003; 300(4):832-8. DOI: 10.1016/s0006-291x(02)02916-9. View

20.

Thiagalingam S, Cheng K, Lee H, Mineva N, Thiagalingam A, Ponte J . Histone deacetylases: unique players in shaping the epigenetic histone code. Ann N Y Acad Sci. 2003; 983:84-100. DOI: 10.1111/j.1749-6632.2003.tb05964.x. View