MicroRNA expression profiling of intestinal mucosa tissue predicts multiple crucial regulatory molecules and signaling pathways for gut barrier dysfunction of AIDS patients

Abstract

Human immunodeficiency virus-1 (HIV-1) infection severely damages the gut-associated lymphoid tissue (GALT), the immune system and the gut barrier, which leads to accelerating the disease progression for patients with acquired immune deficiency syndrome (AIDS). Dysregulation of microRNAs (miRNAs) may contribute to this process. However, few studies have investigated the importance of miRNAs in AIDS pathogenesis and progression. The whole miRNA profile of patients with HIV infection from southwest P.R. China and the mode of interaction between HIV-1 and miRNAs remains to be elucidated. Colon mucosal samples were collected from HIV+ patients and HIV− healthy individuals, miRNAs were isolated and subjected to array hybridization in the present study. A total of 476 human and virus-derived microRNAs were significantly altered in the HIV+ group when compared with the control group (P<0.05), which may be involved in the progression to AIDS. Target genes of the significantly altered miRNAs were predicted using the TargetScan, miRbase and miRanda databases and the 10 shared target genes of upregulated miRNAs and the 391 target genes of downregulated miRNAs were selected. As only 10 target genes were predicted for upregulated miRNAs, subsequent GO and KEGG pathway analyses were focused on the 391 target genes of the downregulated miRNAs. The findings of the present study identified a series of crucial pathways, including cell-extracellular matrix interaction and chemokine regulation, which indicated close affinity with CD4+ T cell activation. These pathways, involving genes such as integrin α5, led to a gut barrier dysfunction of patients with HIV. Important miRNAs include hsa-miRNA-32-5p, hsa-miRNA-195-5p, hsa-miRNA-20b-5p, hsa-miRNA-590-5p. The expression levels of the miRNAs and their target genes were confirmed using RT-qPCR. Taking into previous observations, the findings of the present study identified the importance of miRNAs for regulating gut barrier dysfunction via multiple regulatory molecules and signaling pathways, which elucidated the underlying molecular mechanism of gut barrier dysfunction in patients with HIV.

Complement-Opsonized HIV Modulates Pathways Involved in Infection of Cervical Mucosal Tissues: A Transcriptomic and Proteomic Study

“…In addition to receptor-mediated immune suppression, there may also be a regulation of translation of mRNA into protein via miRNAs. miRNA dysregulation has been shown during HIV infection and is also involved in breaches in the gastrointestinal integrity found in HIV-infected individuals ( 81 ). Nonetheless, we did not find these affected in our system, and for the miRNAs with significant fold change in our system, the functions remain unknown.…”

Gene Expression: the Key to Understanding HIV-1 Infection?

“…Among downregulated genes were those involved in cell cycle regulation, epithelial barrier, lipid metabolism, nutrient absorption, and amino acid metabolism (33,76). Several miRNAs (hsa-miRNA-32-5p, hsa-miRNA-195-5p, hsa-miRNA-20b-5p, and hsa-miRNA-590-5p) may have roles in regulating the colonic epithelial barrier and CD4 ϩ T cell activation (77). The findings reflect the structural and functional changes in the gastrointestinal tract resulting from HIV infection, which manifest as symptomatic intestinal dysfunction, nutrient malabsorption and deficiency, and chronic inflammation from epithelial barrier degeneration and microbial translocation.…”

miR‑125b‑5p inhibits cell proliferation by targeting ASCT2 and regulating the PI3K/AKT/mTOR pathway in an LPS‑induced intestinal mucosa cell injury model

“…In addition, it was found that miR-125b-5p contributed to HIV-1 latency in resting primary CD4+ T lymphocytes ( 21 ). A previous miRNA sequencing study from our group showed that multiple miRNAs were abnormally expressed in the intestinal mucosa of HIV/AIDS patients, including miR-125b-5p ( 22 ). However, the functions and mechanisms of miR-125b-5p on intestinal mucosal cell injury remain unclear.…”