Common pathway signature in lung and liver fibrosis.
Fibrosis, a progressive accumulation of extracellular matrix components, encompasses a wide spectrum of distinct organs, and accounts for an increasing burden of morbidity and mortality worldwide. Despite the tremendous clinical impact, the mechanisms governing the fibrotic process are not yet understood, and to date, no clinically reliable therapies for fibrosis have been discovered. Here we applied Regeneration Intelligence, a new bioinformatics software suite for qualitative analysis of intracellular signaling pathway activation using transcriptomic data, to assess a network of molecular signaling in lung and liver fibrosis. In both tissues, our analysis detected major conserved signaling pathways strongly associated with fibrosis, suggesting that some of the pathways identified by our algorithm but not yet wet-lab validated as fibrogenesis related, may be attractive targets for future research. While the majority of significantly disrupted pathways were specific to histologically distinct organs, several pathways have been concurrently activated or downregulated among the hepatic and pulmonary fibrosis samples, providing new evidence of evolutionary conserved pathways that may be relevant as possible therapeutic targets. While future confirmatory studies are warranted to validate these observations, our platform proposes a promising new approach for detecting fibrosis-promoting pathways and tailoring the right therapy to prevent fibrogenesis.
a Atlas Regeneration, Inc. , Winston-Salem , NC , USA.|b Insilico Medicine, Inc., ETC, Johns Hopkins University , Baltimore , MD , USA.
Eugene
E
Makarev
c Department of Otolaryngology-Head & Neck Surgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Evgeny
E
Izumchenko
d Advanced Academic Programs, Johns Hopkins University , Baltimore , MD , USA.
Fumiaki
F
Aihara
c Department of Otolaryngology-Head & Neck Surgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Piotr T
PT
Wysocki
b Insilico Medicine, Inc., ETC, Johns Hopkins University , Baltimore , MD , USA.
Qingsong
Q
Zhu
e The Biogerontology Research Foundation , London , UK.
Anton
A
Buzdin
c Department of Otolaryngology-Head & Neck Surgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
David
D
Sidransky
b Insilico Medicine, Inc., ETC, Johns Hopkins University , Baltimore , MD , USA.|f Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine , Winston-Salem , NC , USA.
Alex
A
Zhavoronkov
a Atlas Regeneration, Inc. , Winston-Salem , NC , USA.|g Pathway Pharmaceuticals, Ltd , Hong Kong , Hong Kong.
Anthony
A
Atala
D020869:Gene Expression Profiling; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D012984:Software
IPF; PAS; algorithm; bioinformatics; liver fibrosis; pathway activation; signaling pathway signature