Lin, Yi-Wei; Nhieu, Jennifer; Wei, Chin-Wen; Lin, Yu-Lung; Kagechika, Hiroyuki; Wei, Li-Na published the artcile< Regulation of exosome secretion by cellular retinoic acid binding protein 1 contributes to systemic anti-inflammation>, Electric Literature of 6823-69-4, the main research area is exosome secretion Crabp1 antiinflammation; Crabp1; Exosome; Inflammation; Macrophage; Neuron; RIP140; Retinoic acid.
Intercellular communications are important for maintaining normal physiol. processes. An important intercellular communication is mediated by the exchange of membrane-enclosed extracellular vesicles. Among various vesicles, exosomes can be detected in a wide variety of biol. systems, but the regulation and biol. implication of exosome secretion/uptake remains largely unclear. Cellular retinoic acid (RA) binding protein 1 (Crabp1) knockout (CKO) mice were used for in vivo studies. Extracellular exosomes were monitored in CKO mice and relevant cell cultures including embryonic stem cell (CJ7), macrophage (Raw 264.7) and hippocampal cell (HT22) using Western blot and flow cytometry. Receptor Interacting Protein 140 (RIP140) was depleted by Crispr/Cas9-mediated gene editing. Anti-inflammatory maker was analyzed using qRT-PCR. Clin. relevance was accessed by mining multiple clin. datasets. This study uncovers Crabp1 as a neg. regulator of exosome secretion from neurons. Specifically, RIP140, a pro-inflammatory regulator, can be transferred from neurons, via Crabp1-regulated exosome secretion, into macrophages to promote their inflammatory polarization. Consistently, CKO mice, defected in the neg. control of exosome secretion, have significantly elevated RIP140-containing exosomes in their blood and cerebrospinal fluid, and exhibit an increased vulnerability to systemic inflammation. Clin. relevance of this pathway is supported by patients data of multiple inflammatory diseases. Further, the action of Crabp1 in regulating exosome secretion involves its ligand and is mediated by its downstream target, the MAPK signaling pathway. Conclusions: This study presents the first evidence for the regulation of exosome secretion, which mediates intercellular communication, by RA-Crabp1 signaling. This novel mechanism can contribute to the control of systemic inflammation by transferring an inflammatory regulator, RIP140, between cells. This represents a new mechanism of vitamin A action that can modulate the homeostasis of system-wide innate immunity without involving gene regulation.
Cell Communication and Signaling published new progress about Animal cell (HT22). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Electric Literature of 6823-69-4.
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem