Journal: JCI Insight

Article Title: A potent inhibitor of PAI-1, MDI-2517, mitigates disease severity in a preclinical systemic sclerosis model

doi: 10.1172/jci.insight.195005

Figure Lengend Snippet: ( A ) Comparison of SERPINE1 expression in SSc and healthy control skin biopsy samples from the GEO dataset ( GSE58095 ). ( B ) Correlation analysis of modified Rodnan skin scores (mRSS) versus SERPINE1 expression from the data in A . ( C ) Enriched signature for expression of extracellular matrix (ECM) genes along with expression of the myofibroblast marker COL8A1 , and SERPINE1 (PAI-1) expression in SSc skin on the 10x Visium spatial platform (data representative of n = 4). ( D ) Violin plots of SERPINE1 expression in controls versus SSc skin across single-cell RNA-seq data from different cellular populations (top) and fibroblast subsets (bottom) ( n = 18 healthy controls, n = 22 SSc patients). ( E ) Enriched biological processes in SERPINE1 + versus SERPINE1 – COL8A1 myofibroblasts. ( F ) IHC of PAI-1 in SSc skin biopsy (data representative of n = 6). ( G ) IHC of PAI-1 in skin biopsy from a healthy volunteer. Scale bars: 500 μm on overall biopsy, 50 μm on the insets. **** P < 0.0001 by 2-tailed Mann-Whitney test in A . P = 0.0003 by Spearman’s r correlation test in B .

Article Snippet: Optimization of tissue permeabilization was performed on 20 μm sections using a Visium Spatial Tissue Optimization Reagents Kit (10x Genomics), which established an optimal permeabilization time of 9 minutes.

Techniques: Comparison, Expressing, Control, Modification, Marker, Single Cell, RNA Sequencing, MANN-WHITNEY