Abstract
Aims: To explore the explicit role of fibronectin (FN) isforms in atherosclerotic lesions and the underlying mechanisms. Methods and Results: Inducible stable expression was performed, and similar results were observed between EDA<sup>+</sup>FN (FN containing EDA domain) and EDA<sup>-</sup>FN (FN devoid of EDA domain). FN isforms could trigger endoplasmic reticulum (ER) stress, thereby leading to lipid accumulation in cultured Raw264.7 cells. FN isforms-induced gene expression and lipid accumulation were inhibited by a chemical chaperone 4-phenyl butyric acid (PBA) or by overexpression of the ER chaperone, GRP78/BiP, demonstrating a direct role of ER stress in activation of cholesterol/triglyceride biosynthesis. Moreover, activation of the sterol regulatory element binding protein-2 (SREBP2) was found to be downstream of ER stress, and this activation was affirmed to account for the intracellular accumulation of cholesterol using RNAi technique. Conclusion: our study suggests that enhanced FN in lesions facilitates foam cell formation due to dysregulation of the endogenous sterol response pathway by activation of ER stress, and confirms that EDA<sup>+</sup>FN has no more pro-atherogenic role than EDA-FN in triggering ER stress.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.