BAG6 is a novel player in controlling nonalcoholic steatohepatitis: result from a comprehensivein-silicostudy

Abstract

Nonalcoholic steatohepatitis, or NASH, is a multifactorial disease characterized by hepatic lipid accumulation, inflammation, cell death, and fibrosis, and an efficacious pharmaceutical intervention for this is yet to be discovered. The present study aims to identify potential targets capable of reversing the disease-specific molecular alterations and elucidate their possible action mechanism. Our study uses combinations of different methods, such as genome-scale metabolic modelling, directional protein-protein interaction network, connectivity map, and network controllability, to identify potential targets in NASH. Our approach yielded three promising targets, BAG6, CASP3, and CYCS, and captured their effects on inflammation, fibrosis, steatosis, and apoptosis. The association of CASP3 and CYCS with NASH are already reported in the literature. So BAG6 was selected as a novel target. In the Huh-7 cell-line, its ablation reduced fatty acid accumulation and decreased levels of NASH-signature transcripts, supporting our hypothesis on BAG6 as a potential NASH target.

Network controllability analysis reveals the antiviral potential of Etravirine against Hepatitis E Virus infection

“…DEGs were identified at three-fold change cut offs (1.5, 2 and 2.5, Figure 1a). CMap and network controllability analysis was done as described (26). Briefly, the DEGs from different cut offs were independently analysed in CMap database and genes which showed a connectivity score cut-off of -90 or less were selected (56).…”

“…Control theory analysis of the resulting data helps identify the network's most fragile nodes. Therefore, a potential target obtained through a combination of CMap and network controllability analysis will not only regulate the network dynamics, but also, likely induce a transition in the state of the system from "disease" to "healthy" (26).…”