Journal: Cell Reports

Article Title: Single-Cell Transcriptomics Uncovers Zonation of Function in the Mesenchyme during Liver Fibrosis

doi: 10.1016/j.celrep.2019.10.024

Figure Lengend Snippet: Targeting of LPAR1 on Collagen-Producing HSCs Inhibits Liver Fibrosis (A) Violin plots: expression of fibrillar collagen genes ( Col1a1 , Col1a2 , and Col3a1 ) and Lpar1 in PaHSCs versus CaHSCs following acute (72 h post single CCl 4 injection; top) and chronic (6 weeks CCl 4 ; bottom) liver injury. (B) Violin plot: expression of Lpar1 in hepatic mesenchymal cells (Mes), endothelial cells (Endo), and leucocytes (Leuc) from chronic liver. (C) t-SNE visualization (left): 2,210 mesenchymal cells from healthy and cirrhotic human livers cluster into three subpopulations. t-SNE visualization (right): cells from healthy (gray) and cirrhotic (pink) liver. (D) Violin plots: expression of fibrillar collagen genes (COL1A1, COL1A2, and COL3A1) and LPAR1 across the three human mesenchymal subpopulations. (E) Bar plot: LPAR1 gene expression (RNA-seq) from human FFPE liver samples at different stages of NASH (F1, n = 40; F2, n = 31; F3/4, n = 24); error bars SEM. Kruskal-Wallis test, ∗∗ p < 0.01. (F) Scatterplot: correlation of LPAR1 expression (y axis) and fibrillar collagen genes (COL1A1, COL1A2, and COL3A1, x axis). r values are Spearman correlation coefficients, p < 0.0001. (G) Representative images of livers from control, CDHFD, and CDHFD + LPAR1 antagonist (LPAR1-i; 30 mg/kg, BID) rodents stained for collagen stain picrosirius red stain (PSR; top) and immunostained for myofibroblast activation marker alpha-smooth-muscle actin (αSMA; bottom). Scale bar, 100 μm. Bar plots (right): percentage area of tissue positive for PSR (top) or αSMA (bottom) (control, n = 11; vehicle, n = 9; LPAR1-i, n = 14); error bars SEM. Mann-Whitney test, ∗∗ p < 0.01, ∗∗∗∗ p < 0.0001. (H) Bar plot: hydroxyproline (HYP) levels in liver lysates from control, CDHFD (vehicle), and CDHFD + LPAR1 antagonist (LPAR1-i; 30 mg/kg) rodents (control, n = 11; vehicle, n = 9; LPAR1-i, n = 15); error bars SEM. Mann-Whitney test, ∗∗∗∗ p < 0.0001. See also Figure S10 .

Article Snippet: TWNT4 cells ( ) (courtesy of Bryan Fuchs, PhD) were plated on 96-well optical plates (Greiner Bio-One; 655946) in complete media (DMEM, (GIBCO; 15-018-CM), 10% FBS, (Hyclone; SH30088.03), Penicillin-streptomycin-glutamate (GIBCO; 10378)), serum-starved overnight, was pretreated with DMSO or 1μM LPAR1 antagonist (BMS-986020) ( ) (Medchem Express; HY-100619) for 30 minutes, then treated with 0.1% BSA (control) or 10μM 18:2 LPA (Avanti Polar Lipids; 857138) for 20 minutes.

Techniques: Expressing, Injection, RNA Sequencing Assay, Control, Staining, Activation Assay, Marker, MANN-WHITNEY

Journal: Journal of pharmacological sciences

Article Title: A novel lysophosphatidic acid receptor 1 antagonist with high brain penetrability has a curative effect in the empathic pain-related fibromyalgia model.

doi: 10.1016/j.jphs.2025.03.012

Figure Lengend Snippet: Fig. 1. Chemical properties of Compound A (A) Structural information of Compound A (B) Dose-dependent inhibition of Compound A in LPA-induced 35S-GTPγS binding to the cell membrane. (C) Dose-dependent inhibition of Compound A in Ca2+ influx. (D) Specific binding evaluation of Compound A on GPCR in β-arrestin assay. LPA1, 2, 3, 5: lysophosphatidic acid receptor 1, 2, 3, 5, S1P1, 4: sphingosine-1-phosphate receptor 1, 4.

Article Snippet: BMS-986020, an LPA1 antagonist9 was purchased from MCE (Monmouth Junction, NJ, USA).

Techniques: Inhibition, Binding Assay, Membrane, Beta-Arrestin Assay