TY - JOUR
T1 - CD31 orchestrates metabolic regulation in autophagy pathways of rheumatoid arthritis
AU - Cheung, Kenneth Chat Pan
AU - Ma, Jiao
AU - Wang, Lu
AU - Chen, Xingxuan
AU - Fanti, Silvia
AU - Li, Mingzhang
AU - Azevedo, Loiola Rodrigo
AU - Gosselet, Fabien
AU - Shen, Hao
AU - Zheng, Xiaojiao
AU - Lu, Aiping
AU - Jia, Wei
PY - 2024/9
Y1 - 2024/9
N2 - Synovitis is characterized by a distinctmetabolic profile featuring the accumulation of lactate, a byproduct of cellular metabolism within inflamed joints. This study reveals that the activation of the CD31 signal by lactate instigates a metabolic shift, specifically initiating endothelial cell autophagy. This adaptive process plays a pivotal role in fulfilling the augmented energy and biomolecule demands associated with the formation of new blood vessels in the synovium of Rheumatoid Arthritis (RA). Additionally, the amino acid substitutions in the CD31 cytoplasmic tail at the Y663F and Y686F sites of the immunoreceptor tyrosine-based inhibitory motifs (ITIM) alleviate RA. Mechanistically, this results in the downregulation of glycolysis and autophagy pathways. These findings significantly advance our understanding of potential therapeutic strategies for modulating these processes in synovitis and, potentially, other autoimmune diseases.
AB - Synovitis is characterized by a distinctmetabolic profile featuring the accumulation of lactate, a byproduct of cellular metabolism within inflamed joints. This study reveals that the activation of the CD31 signal by lactate instigates a metabolic shift, specifically initiating endothelial cell autophagy. This adaptive process plays a pivotal role in fulfilling the augmented energy and biomolecule demands associated with the formation of new blood vessels in the synovium of Rheumatoid Arthritis (RA). Additionally, the amino acid substitutions in the CD31 cytoplasmic tail at the Y663F and Y686F sites of the immunoreceptor tyrosine-based inhibitory motifs (ITIM) alleviate RA. Mechanistically, this results in the downregulation of glycolysis and autophagy pathways. These findings significantly advance our understanding of potential therapeutic strategies for modulating these processes in synovitis and, potentially, other autoimmune diseases.
KW - Autophagy
KW - CD31
KW - Endothelium
KW - Glycolysis and oxidative phosphorylation
KW - Inflammation
KW - Rheumatoid arthritis
UR - http://www.scopus.com/inward/record.url?scp=85200815158&partnerID=8YFLogxK
U2 - 10.1016/j.phrs.2024.107346
DO - 10.1016/j.phrs.2024.107346
M3 - Journal article
SN - 1043-6618
VL - 207
JO - Pharmacological Research
JF - Pharmacological Research
M1 - 107346
ER -
