%0 Figure %A Renaud, Ludivine %A da Silveira, Willian A. %A Takamura, Naoko %A Hardiman, Gary %A Feghali-Bostwick, Carol %D 2020 %T Image_4_Prominence of IL6, IGF, TLR, and Bioenergetics Pathway Perturbation in Lung Tissues of Scleroderma Patients With Pulmonary Fibrosis.PDF %U https://frontiersin.figshare.com/articles/figure/Image_4_Prominence_of_IL6_IGF_TLR_and_Bioenergetics_Pathway_Perturbation_in_Lung_Tissues_of_Scleroderma_Patients_With_Pulmonary_Fibrosis_PDF/11959455 %R 10.3389/fimmu.2020.00383.s006 %2 https://frontiersin.figshare.com/ndownloader/files/21957438 %K scleroderma %K systemic sclerosis %K pulmonary fibrosis %K idiopathic %K microarray %K interstitial lung disease %X

Scleroderma-associated pulmonary fibrosis (SSc-PF) and idiopathic pulmonary fibrosis (IPF) are two of many chronic fibroproliferative diseases that are responsible for nearly 45% of all deaths in developed countries. While sharing several pathobiological characteristics, they also have very distinct features. Currently no effective anti-fibrotic treatments exist that can halt the progression of PF or reverse it. Our goal is to uncover potential gene targets for the development of anti-fibrotic therapies efficacious in both diseases, and those specific to SSc-PF, by identifying universal pathways and molecules driving fibrosis in SSc-PF and IPF tissues as well as those unique to SSc-PF. Using DNA microarray data, a meta-analysis of the differentially expressed (DE) genes in SSc-PF and IPF lung tissues (diseased vs. normal) was performed followed by a full systems level analysis of the common and unique transcriptomic signatures obtained. Protein-protein interaction networks were generated to identify hub proteins and explore the data using the centrality principle. Our results suggest that therapeutic strategies targeting IL6 trans-signaling, IGFBP2, IGFL2, and the coagulation cascade may be efficacious in both SSc-PF and IPF. Further, our data suggest that the expression of matrikine-producing collagens is also perturbed in PF. Lastly, an overall perturbation of bioenergetics, specifically between glycolysis and fatty acid metabolism, was uncovered in SSc-PF. Our findings provide insights into potential targets for the development of anti-fibrotic therapies that could be effective in both IPF and SSc-PF.

%I Frontiers