microRNA Regulation of Peritoneal Cavity Homeostasis in Peritoneal Dialysis

Figure 1

miRNA dysregulation in peritoneal dialysis. (a) miRNA biogenesis pathway. miRNAs are transcribed by RNA polymerase (Pol II) or Pol III as primary miRNA (pri-miRNA) transcripts that are processed by Drosha to generate precursor miRNAs (pre-miRNAs). Pre-miRNA hairpins are transported by Exportin-5 to the cytoplasm, where mature miRNAs are generated by Dicer, and incorporated into the RNA-induced silencing complex (RISC). miRNA-RISC complexes bind to the 3′ untranslated regions (3′ UTRs) of target mRNAs by partial complementarity, resulting in repression of translation and/or mRNA degradation. (b) Peritoneal mesothelial-to-mesenchymal transition (MMT) is associated with PD therapy. Healthy peritoneal mesothelial cells (PMCs; left hand side) undergo morphological changes during PD-driven MMT, invading the submesothelium where they contribute to angiogenesis and fibrosis and increase extracellular matrix (ECM) components deposition during PD therapy (right hand side). (c) Dysregulated miRNA expression resulting from PD therapy. Only miRNAs for which specific evidence in HPMCs exists are shown.