Possible effects of fibroblast growth factor 21 on vascular calcification via suppressing activating transcription factor 4 mediated apoptosis and osteogenic transformation in rats

Abstract

Vascular calcification (VC), a significant risk factor of many cardio‐cerebral vascular diseases, is a perplexing issue with no effective treatment in clinical work up to now. Endoplasmic reticulum stress (ERS) mediated apoptosis has been proved to be a significant mechanism for initiating VC process. Activating transcription factor 4 (ATF4), a key transcription factor of ERS, is most closely associated with VC. Fibroblast growth factor 21 (FGF21), an atypical member of the FGFs family, has a protective biological function in various metabolic diseases by ERS pathways. However, the possible effects of FGF21 on VC by regulating ERS, especially through the ATF4 pathway, is still unclear. Our research provides the first evidence that exogenous FGF21 treatment can alleviate the vitamin D3 plus nicotine‐induced VC at least in part via suppressing ATF4 mediated apoptosis and osteogenic transformation in rats.

Sargassum polysaccharide attenuates osteoarthritis in rats and is associated with the up-regulation of the ITGβ1-PI3K-AKT signaling pathway

“…Regarding ERN1, research indicates that ERN1 mRNA is the actual target of hcmv-miR-UL148D and its encoded protein IRE1α is translationally repressed by the overexpression of hcmv-miR-UL148D resulting in the attenuation of apoptosis [ 72 ]. Regarding ATF4, research has demonstrated that activated transcription factor 4 (ATF4) plays a pivotal role as the key transcription factor in ERS [ 73 ], and is at least partially implicated in ERS-mediated apoptosis [ 74 ]. Although the studies [ 73 , 74 ] focus on vascular calcification rather than osteoarthritis, they underscore the critical role of ATF4 in modulating endoplasmic reticulum stress and apoptosis.…”

“…Regarding ATF4, research has demonstrated that activated transcription factor 4 (ATF4) plays a pivotal role as the key transcription factor in ERS [ 73 ], and is at least partially implicated in ERS-mediated apoptosis [ 74 ]. Although the studies [ 73 , 74 ] focus on vascular calcification rather than osteoarthritis, they underscore the critical role of ATF4 in modulating endoplasmic reticulum stress and apoptosis. Concerning Bid, the study indicates that the concurrent elevation of Bim, Bid and Bad, along with reduced levels of Bcl-2 and Bcl-xl may render cells more susceptible to apoptosis during sepsis.…”