Small Chain Fatty Acid Phenylbutyric Acid Alleviated Inflammation-Induced Endoplasmic Reticulum Stress in Endothelial Cells

Endothelial cells (EC) have dynamic properties and high plasticity in response to microenvironmental change. A proinflammatory cytokine such as tumor necrotizing factor-α (TNF-α) can induce EC phenotype shift to osteoinduction properties by releasing a potent osteogenic cytokine, namely bone morpho...

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Main Author: Oski Illiandri
Format: Article
Language:English
Published: Tehran University of Medical Sciences 2021-02-01
Series:Acta Medica Iranica
Subjects:
Online Access:https://acta.tums.ac.ir/index.php/acta/article/view/8671
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spelling doaj-f0055939dbb7412e9494a07ca8d36f412021-09-11T04:04:43ZengTehran University of Medical SciencesActa Medica Iranica0044-60251735-96942021-02-0159210.18502/acta.v59i2.5573Small Chain Fatty Acid Phenylbutyric Acid Alleviated Inflammation-Induced Endoplasmic Reticulum Stress in Endothelial CellsOski Illiandri0Department of Biomedicine, School of Medicine, University of Lambung Mangkurat, Banjarmasin, South Kalimantan, Indonesia. Endothelial cells (EC) have dynamic properties and high plasticity in response to microenvironmental change. A proinflammatory cytokine such as tumor necrotizing factor-α (TNF-α) can induce EC phenotype shift to osteoinduction properties by releasing a potent osteogenic cytokine, namely bone morphogenetic protein 2 (BMP2). Normally BMP2 acts as an osteoblast stimulating factor in bone and cartilage tissue. BMP2 activation in vascular tissue will invite osteoblast recruitment and mineralization and generated pathological vascular stiffening and calcification. Recently, endoplasmic reticulum stress (ERS) has been emerging as a new target therapy in many vascular diseases such as vascular stiffening and calcification. Some short-chain fatty acid like 4-phenyl butyric acid has been shown had anti-ERS properties. However, the role of 4-phenyl butyric acid in BMP2 inhibition in endothelial cells is still poorly understood. Hence, we investigated the role of 4-phenyl butyric acid in inflammation-induced BMP2 expression in human vein derived endothelial cells. Endothelial cells obtained from a baby born umbilical vein were cultured and pre-treated with TNF-α (5 ng/ml) as inflammation precondition. Multiple doses of 4-phenyl butyrate acid (4-PBA) 1 nM/mL, 2 nM/mL, and 3 nM/m were used as ERS inhibitors. The expression of two ERS biomarkers, glucose-related protein-8 (GRP78) and activating transcription factor-6 (ATF6), were measured. Statistical analysis was done using one-way ANOVA and Kruskal Wallis tests, and P<0.01 considered as significant. 4-PBA decrease luminal BMP2 at dose one nM/L, GRP78 at dose 1 nM/L, and translocated ATF6 expression at dose 1 nM/L in endothelial culture dose-dependently. Short-chain fatty acid 4-phenylbutyrate acid decreases luminal ERS marker GRP78 and translocated ATF6 expression in endothelial culture. ERS has a role in osteoinductive phenotype shifting in inflammation endothelial cells, which was the novelty of this research. Further research needs to elucidate ERS inhibition in in vivo experiment https://acta.tums.ac.ir/index.php/acta/article/view/8671Bone morphogenetic protein-2Endoplasmic reticulum stressEndothelial cellsSmall chain fatty acidTumor necrosis factor-α
collection DOAJ
language English
format Article
sources DOAJ
author Oski Illiandri
spellingShingle Oski Illiandri
Small Chain Fatty Acid Phenylbutyric Acid Alleviated Inflammation-Induced Endoplasmic Reticulum Stress in Endothelial Cells
Acta Medica Iranica
Bone morphogenetic protein-2
Endoplasmic reticulum stress
Endothelial cells
Small chain fatty acid
Tumor necrosis factor-α
author_facet Oski Illiandri
author_sort Oski Illiandri
title Small Chain Fatty Acid Phenylbutyric Acid Alleviated Inflammation-Induced Endoplasmic Reticulum Stress in Endothelial Cells
title_short Small Chain Fatty Acid Phenylbutyric Acid Alleviated Inflammation-Induced Endoplasmic Reticulum Stress in Endothelial Cells
title_full Small Chain Fatty Acid Phenylbutyric Acid Alleviated Inflammation-Induced Endoplasmic Reticulum Stress in Endothelial Cells
title_fullStr Small Chain Fatty Acid Phenylbutyric Acid Alleviated Inflammation-Induced Endoplasmic Reticulum Stress in Endothelial Cells
title_full_unstemmed Small Chain Fatty Acid Phenylbutyric Acid Alleviated Inflammation-Induced Endoplasmic Reticulum Stress in Endothelial Cells
title_sort small chain fatty acid phenylbutyric acid alleviated inflammation-induced endoplasmic reticulum stress in endothelial cells
publisher Tehran University of Medical Sciences
series Acta Medica Iranica
issn 0044-6025
1735-9694
publishDate 2021-02-01
description Endothelial cells (EC) have dynamic properties and high plasticity in response to microenvironmental change. A proinflammatory cytokine such as tumor necrotizing factor-α (TNF-α) can induce EC phenotype shift to osteoinduction properties by releasing a potent osteogenic cytokine, namely bone morphogenetic protein 2 (BMP2). Normally BMP2 acts as an osteoblast stimulating factor in bone and cartilage tissue. BMP2 activation in vascular tissue will invite osteoblast recruitment and mineralization and generated pathological vascular stiffening and calcification. Recently, endoplasmic reticulum stress (ERS) has been emerging as a new target therapy in many vascular diseases such as vascular stiffening and calcification. Some short-chain fatty acid like 4-phenyl butyric acid has been shown had anti-ERS properties. However, the role of 4-phenyl butyric acid in BMP2 inhibition in endothelial cells is still poorly understood. Hence, we investigated the role of 4-phenyl butyric acid in inflammation-induced BMP2 expression in human vein derived endothelial cells. Endothelial cells obtained from a baby born umbilical vein were cultured and pre-treated with TNF-α (5 ng/ml) as inflammation precondition. Multiple doses of 4-phenyl butyrate acid (4-PBA) 1 nM/mL, 2 nM/mL, and 3 nM/m were used as ERS inhibitors. The expression of two ERS biomarkers, glucose-related protein-8 (GRP78) and activating transcription factor-6 (ATF6), were measured. Statistical analysis was done using one-way ANOVA and Kruskal Wallis tests, and P<0.01 considered as significant. 4-PBA decrease luminal BMP2 at dose one nM/L, GRP78 at dose 1 nM/L, and translocated ATF6 expression at dose 1 nM/L in endothelial culture dose-dependently. Short-chain fatty acid 4-phenylbutyrate acid decreases luminal ERS marker GRP78 and translocated ATF6 expression in endothelial culture. ERS has a role in osteoinductive phenotype shifting in inflammation endothelial cells, which was the novelty of this research. Further research needs to elucidate ERS inhibition in in vivo experiment
topic Bone morphogenetic protein-2
Endoplasmic reticulum stress
Endothelial cells
Small chain fatty acid
Tumor necrosis factor-α
url https://acta.tums.ac.ir/index.php/acta/article/view/8671
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