Oxidative Stress-Induced Growth Inhibitor (OSGIN1), a Target of X-Box-Binding Protein 1, Protects Palmitic Acid-Induced Vascular Lipotoxicity through Maintaining Autophagy

Chong Sun Khoi, Cai Qin Xiao, Kuan Yu Hung, Tzu Yu Lin, Chih Kang Chiang

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Saturated free fatty acids (FFAs) strongly correlate with metabolic syndromes and are well-known risk factors for cardiovascular diseases (CVDs). The mechanism of palmitic acid (PA)-induced vascular lipotoxicity under endoplasmic reticulum (ER) stress is unknown. In the present paper, we investigate the roles of spliced form of X-box-binding protein 1 (XBP1s) target gene oxidative stress-induced growth inhibitor 1 (OSGIN1) in PA-induced vascular dysfunction. PA inhibited the tube formation assay of primary human umbilical vein endothelial cells (HUVECs). Simultaneously, PA treatment induced the XBP1s expression in HUVECs. Attenuate the induction of XBP1s by silencing the XBP1s retarded cell migration and diminished endothelial nitric oxide synthase (eNOS) expression. OSGIN1 is a target gene of XBP1s under PA treatment. The silencing of OSGIN1 inhibits cell migration by decreasing phospho-eNOS expression. PA activated autophagy in endothelial cells, inhibiting autophagy by 3-methyladenine (3-MA) decreased endothelial cell migration. Silencing XBP1s and OSGIN1 would reduce the induction of LC3 II; therefore, OSGIN1 could maintain autophagy to preserve endothelial cell migration. In conclusion, PA treatment induced ER stress and activated the inositol-requiring enzyme 1 alpha–spliced XBP1 (IRE1α–XBP1s) pathway. OSGIN1, a target gene of XBP1s, could protect endothelial cells from vascular lipotoxicity by regulating autophagy.

Original languageEnglish
Article number992
JournalBiomedicines
Volume10
Issue number5
DOIs
Publication statusPublished - May 2022
Externally publishedYes

Keywords

  • autophagy
  • endothelial cells
  • eNOS
  • OSGIN1
  • palmitic acid
  • unfolded protein response
  • XBP1s

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology

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