Biotechnologists have yet to discover the therapeutic key to the frustrating disease that is non-alcoholic steatohepatitis (NASH). Now, researchers from the University of Michigan have identified an interesting hormone that could unblock the worse liver disease that NASH is a harbinger of.
The findings, published Monday in Cell Metabolism, focus on a hormone primarily secreted by fat cells that has been found to be a checkpoint for further progression of liver disease.
The team led by Jiandie Lin previously revealed that NRG4 is a critical marker of liver disease progression in NASH mice and that elevated levels can protect against NASH. Now, the same team has backed up that research, finding that when NASH is already present, a lack of the hormone was associated with a worse case of the disease and more liver tumors.
“Many studies of liver cancer focus on the liver cancer cells themselves: how they multiply and how they evade the immune system,” Lin said in a news release.
To test the effect of the hormone, the team created a mouse model of NASH with the gene knocked out in some mice. In these cases, there was a “significantly increased incidence of tumors” and the number of tumors was 2.6 times higher compared to the control group without the gene knockout.
The researchers also found that without NRG4, there is a likely exacerbation of “pathological reprogramming of the T-cell transcriptome under conditions of metabolic stress.” In addition, the T cells that responded to the environment were more exhausted than in the control group.
As the NASH setbacks pile up in pharma, Regeneron thinks it has found a target that matters
Conversely, when NRG4 was overexpressed, there was a reduction in the number of tumors in the mice, specifically larger tumors. The authors concluded that the gene plays an important role “in the modulation of the immune microenvironment of the liver and the development of NASH-associated [hepatocellular carcinoma].”
The impetus for the study was to try and assess how NASH drives molecular and cellular changes. The new knowledge about NRG4 came after the researchers found that in mice with NASH, T cell function was impaired and macrophages appeared to adopt behaviors appropriate to the tumor microenvironment. The researchers say the subsequent results from the mouse model inspire further research into the gene as a potential therapeutic target.
provide an attractive target for therapeutic intervention in NASH-associated HCC,” they wrote. .
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