Analysis of time-resolved immunological phases in the NIF mouse model for liver fibrosis.
A time-course, bulk RNA-sequencing analysis of liver and kidney tissue from NIF mice was performed to identify the dynamics of key processes contributing to the pathogenesis. Transcriptomics profiling of the NIF mouse revealed a gradual transition from an initially reactive inflammatory response to a regenerative, pro-fibrotic inflammatory response suggesting new avenues for treatment strategies that focus on immunological targets. Despite the lack of metabolic stress induced liver phenotype, a large similarity between the NIF mouse and the immunological phase of human MASH was detected. The translational value was further confirmed through comparative analyses with MASH patients and additional animal models. Overall design: Comparative gene expression analysis was performed using data obtained from RNA-seq of NIF and control 24abNOD mice at three different ages, 3 weeks, 6 weeks and 18 weeks.