Protein l-isoaspartyl methyltransferase (PIMT/PCMT1), an
enzyme repairing
isoaspartate residues in
peptides and
proteins that result from the spontaneous decomposition of normal l-aspartyl and l-asparaginyl residues during aging, has been revealed to be involved in
neurodegenerative diseases (NDDs) and diabetes. However, the molecular mechanisms for a putative association of PIMT dysfunction with these diseases have not been clarified. Our study aimed to identify differentially expressed
microRNAs (
miRNAs) in the brain and kidneys of PIMT-deficient mice and uncover the epigenetic mechanism of PIMT-involved NDDs and
diabetic nephropathy (DN). Differentially expressed
miRNAs by sequencing underwent target prediction and enrichment analysis in the brain and kidney of PIMT knockout (KO) mice and age-matched wild-type (WT) littermates. Sequence analysis revealed 40 differentially expressed
miRNAs in the PIMT KO mouse brain including 25 upregulated
miRNAs and 15 downregulated
miRNAs. In the PIMT KO mouse kidney, there were 80 differentially expressed
miRNAs including 40 upregulated
miRNAs and 40 downregulated
miRNAs. Enrichment analysis and a systematic literature review of differentially expressed
miRNAs indicated the involvement of PIMT deficiency in the pathogenesis in NDDs and DN. Some overlapped differentially expressed
miRNAs between the brain and kidney were quantitatively assessed in the brain, kidney, and serum-derived exosomes, respectively. Despite being preliminary, these results may aid in investigating the pathological hallmarks and identify the potential therapeutic targets and
biomarkers for PIMT dysfunction-related NDDs and DN.