Integrated analysis of microRNA and mRNA expression profiles in splenomegaly induced by non-cirrhotic portal hypertension in rats

Abstract

The spleen plays an important role in the immune and hematopoietic systems. Splenomegaly is a frequent consequence of portal hypertension, but the underlying molecular and cellular mechanisms remain to be fully elucidated. In this study, we have performed a whole-genome microarray analysis combined with histological examination in enlarged spleens isolated from rats with partial portal vein ligation (PPVL) surgery to provide comprehensive profiles of microRNAs and their target mRNAs with a focus on their potential biological functions. A total of 964 mRNAs and 30 microRNAs showed significant differential expression in the spleens of PPVL rats compared to rats undergoing a sham procedure. Twenty-two down-regulated microRNAs were associated with significantly increased genes highly involved in fibrogenic activity and cell proliferation/migration (e.g., Ctgf, Serpine1, Col1a1). Consistently, histological analyses demonstrated increased splenic fibrosis and cell proliferation in the spleens of PPVL rats. Eight up-regulated microRNAs were associated with suppression of genes that are related to interferon-mediated antiviral activity in innate immune responses (e.g., Irf7, Dhx58). In conclusion, we determined a specific microRNA-mRNA network potentially implicated in the tissue fibrosis and cell proliferation in portal hypertension-induced splenomegaly. Our findings provide new insight into the mechanisms for regulation of spleen structure and function.