GSE241894 Comparison of biochemical pathways affected by treatment with 4-methylumbelliferone and siRNA mediated knock down reveals hyaluronan synthase type 2 as a key pharmacological target in liver fibrosis

Contributors : Noreen Halimani ; Mikhail Nesterchuk ; Alexandra A Tsitrina ; Marat Sabirov ; Irina N Andreichenko ; Nataliya O Dashenkova ; Alexey M Kulikov ; Timofei S Zatsepin ; Roman A Romanov ; Arsen S Mikaelyan ; Yuri V KotelevtsevSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusHepatic fibrosis is a morbid pathology with unmet medical need. 4- methylumbelliferone (4-MU), an inhibitor of hyaluronan (HA) synthesis was shown to be safe in phase one clinical trials. To support drug development, it is essential to decipher 4-MU ’s pharmacological targets. Here, we compared the effects of 4-MU and siRNA to hyaluronan synthase type 2(siHAS2) on CCl4 induced liver fibrosis in mice. Transcriptomic analysis allowed us to identify converging pathways associated with downstream HA signaling in fibrosis. Both 4-MU and siHAS2 red uced collagen and HA deposition as well as cellular and molecular markers of hepatic damage. Functional annotation of siHAS2 specific DEGs revealed attenuation of extracellular matrix (ECM) associated pathways whilst 4MU specific DEGs were enriched in lipid, bile metabolism and cell cycle. 4MU and s iHAS2 shared 405 common upregulated and 628 common down regulated genes. These genes were associated with xenobiotic detoxification, cholesterol metabolism, mitosis, response to endoplasmic reticulum stress, RNA processing and myeloid leukocyte migration. Our data reveal HAS2 is an important pharmac ological target for s...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research