Purpose: To evaluate the effects of valproic acid (VPA), a histone deacetylase inhibitor (HDACI), on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal Müller cells under hypoxic conditions.
Methods: Chemical hypoxia was induced in human retinal Müller cells (MIO-M1) by treatment with increasing concentrations of cobalt(II) chloride (CoCl). Müller cells were also treated with a set concentration of CoCl, along with various concentrations of VPA. The expression of HIF-1α and VEGF in the treated Müller cells was determined by enzyme-linked immunosorbent assay.
Results: Exposure of human retinal Müller cells to increasing concentrations of CoCl produced a dose-dependent increase in HIF-1α expression. The addition of increasing concentrations of VPA lead to a dose-dependent decrease in expression of HIF-1α and VEGF in Müller cells exposed to a set concentration of CoCl.
Conclusions: HDACI VPA downregulated the expressions of HIF-1α and VEGF in human retinal Müller cells under hypoxic conditions. Using HDACI to target HIF-1α expression in Müller cells could be a new therapeutic strategy for the treatment of retinal vascular diseases.
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http://dx.doi.org/10.3341/kjo.2017.31.1.80 | DOI Listing |
Arch Med Res
July 2019
Department of Surgery, School of Medicine, Complutense University of Madrid, Madrid, Spain.
Chronic inflammatory liver disease with an acute deterioration of liver function is named acute-on-chronic inflammation and could be regulated by the metabolic impairments related to the liver dysfunction. In this way, the experimental cholestasis model is excellent for studying metabolism in both types of inflammatory responses. Along the evolution of this model, the rats develop biliary fibrosis and an acute-on-chronic decompensation.
View Article and Find Full Text PDFCells
June 2019
Department of Surgery, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
Portal hypertension is a common complication of liver disease, either acute or chronic. Consequently, in chronic liver disease, such as the hypertensive mesenteric venous pathology, the coexisting inflammatory response is classically characterized by the splanchnic blood circulation. However, a vascular lymphatic pathology is produced simultaneously with the splanchnic arterio-venous impairments.
View Article and Find Full Text PDFClin Res Hepatol Gastroenterol
October 2019
Department of Surgery, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain. Electronic address:
Introduction: Splanchnic mast cells increase in chronic liver and in acute-on-chronic liver diseases. We administered Ketotifen, a mast cell stabilizer, and measured the mast cells in the splanchnic organs of cholestatic rats.
Material And Methods: These groups were studied: sham-operated rats (S; n = 15), untreated microsurgical cholestasic rats (C; n = 20) and rats treated with Ketotifen: early (SK-e; n = 20 and CKe; n = 18), and late (SK-l; n = 15 and CK-l; n = 14).
Inflamm Res
February 2019
Department of Surgery, School of Medicine, Complutense University of Madrid, Plaza de Ramón y Cajal s.n., 28040, Madrid, Spain.
Background: In mammals, inflammation is required for wound repair and tumorigenesis. However, the events that lead to inflammation, particularly in non-healing wounds and cancer, are only partly understood.
Findings: Mast cells, due to their great plasticity, could orchestrate the inflammatory responses inducing the expression of extraembryonic programs of normal and pathological tissue formation.
Inflamm Res
February 2018
Department of Surgery, School of Medicine, Complutense University of Madrid, Plaza de Ramón y Cajal s.n., 28040, Madrid, Spain.
The inflammatory response expressed after wound healing would be the recapitulation of systemic extra-embryonic functions, which would focus on the interstitium of the injured tissue. In the injured tissue, mast cells, provided for a great functional heterogeneity, could play the leading role in the re-expression of extra-embryonic functions, i.e.
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