Sphingosine-1-phosphate (S1P), a bioactive metabolite of sphingolipid, has an important role in lymphocyte trafficking, immune responses, vascular and embryonic development, cancer, bone homeostasis, etc. S1P is produced intracellularly and then secreted into the circulation to engage in the above physiological or pathological processes by regulating the proliferation, differentiation and survival of target cells; however, the underlying mechanisms of S1P secretion and function remain poorly understood. Recently, Spinster 2 (SPNS2), a newly identified transporter of S1P, was shown to act as a mediator of intracellular S1P release and play an important role in the regulation of S1P. In this review, we focus on the primary biological characteristics and functions of SPNS2 and provide novel insights into the development of therapies for S1P-related disorders.
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http://dx.doi.org/10.1016/j.molimm.2018.08.025 | DOI Listing |
Am J Gastroenterol
January 2025
Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada.
Objective: High body mass index (BMI) may reduce ulcerative colitis (UC) treatment efficacy. Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC. This post hoc analysis assessed treatment outcomes according to BMI in ELEVATE UC 52 and ELEVATE UC 12.
View Article and Find Full Text PDFAnal Chem
January 2025
Department of Bioengineering, University of Washington, SeattleWashington98195, United States.
Cell-to-cell heterogeneity in lipid signaling underlies variations in response and recurrence for many cancers, including leukemias. A highly parallel, miniaturized thin-layer chromatographic platform capable of assaying single cells was developed. Ultrasmall volumes (50 pL) of standard fluorescent lipids were separated with excellent repeatability, reproducibility, and limits of detection.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Department of Neurosurgery West China Hospital, Sichuan University, Chengdu, China.
Resveratrol, a polyphenolic compound known for its diverse biological activities, has demonstrated multiple pharmacological effects, including anti-inflammatory, anti-aging, anti-diabetic, anti-cancer, and cardiovascular protective properties. Recent studies suggest that these effects are partly mediated through the regulation of macrophage polarization, wherein macrophages differentiate into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Our review highlights how resveratrol modulates macrophage polarization through various signaling pathways to achieve therapeutic effects.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
January 2025
George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah; University of Utah Spencer Fox Eccles School of Medicine.
(Pro)renin receptor (PRR) contains overlapping cleavage site for site-1 protease (S1P) and furin for generation of soluble PRR (sPRR). Although S1P-mediated cleavage mediates the release of sPRR, the functional implication of furin-mediated cleavage is unclear. Here we tested whether furin-mediated cleavage was required for the activity of sPRR in activating ENaC in cultured M-1 cells.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of Zoology, Aligarh Muslim University, Aligarh 202002, India. Electronic address:
Small molecules are emerging as potential candidates for treating osteoporosis by activating canonical Wnt signaling. These candidates work either by inhibiting DKK-1, sclerostin, SFRP-1, NOTUM, and S1P lyase or by preventing β-catenin degradation through inhibition of GSK-3β, or by targeting Dvl-CXXC5 and axin/β-catenin interactions. While many of these anti-osteoporotic small molecules are in preclinical development, the paucity of FDA-approved small molecules, or promising candidates, that have progressed to clinical trials for treating bone disorders through this mechanism poses a challenge.
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