mRNA Sequencing Analysis of MCM7 Knockdown in Primary Hepatocytes Under IL-6 Stimulation
Liver fibrosis, marked by excessive extracellular matrix deposition, remains a significant challenge due to its complex and not fully understood mechanisms. This study explores the role of Minichromosome Maintenance Complex Component 7 (MCM7) in the development of liver fibrosis, with a focus on its regulatory network and interactions. We knocked down MCM7 in primary hepatocytes and exposed them to IL-6 to simulate inflammatory conditions. RNA sequencing was then utilized to identify the differentially expressed genes and pathways influenced by MCM7 depletion. The results revealed notable alterations in gene expression, particularly in fibrosis- and inflammation-related pathways. Our study identified MCM7 as a key regulator of IL11 expression through the SHCBP1-RACGAP1-STAT3 signaling pathway, which contributes to the activation of hepatic stellate cells and the advancement of liver fibrosis. These findings underscore the critical role of MCM7 in liver fibrosis by promoting IL11 expression, thereby driving the activation of hepatic stellate cells and the progression of fibrosis. Overall, this research sheds light on a mechanistic pathway where MCM7 plays a pivotal role in liver fibrosis progression through the regulation of IL11 expression under inflammatory conditions. Overall design: To understand the role of MCM7 in fibrotic hepatocytes, we employed shRNA to knock down MCM7 in primary hepatocytes. Following the knockdown, the cells were stimulated with IL-6, and RNA sequencing was conducted to profile gene expression. A comparative analysis was performed on the RNA-seq data from primary hepatocytes, both with and without IL-6 stimulation, to assess the effects of MCM7 knockdown.