| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Outline of Final Research Achievements |
We conducted small RNA microarray for the sera of postpartum cardiomyopathy (PPCM) patients with preeclampsia (PE), or healthy controls. We identified miR-320a/b as disease-specific miRNAs. We searched the target genes for miR-320a/b. Then, we picked up EIF2aK3(PERK). Next, we examined the phenotype of control mice and tissue-specific PERK homogenous knockout (HKO) mice during the perinatal period and performed transcriptome analysis and pathway analysis. Cardiac-specific PERK deletion revealed PPCM phenotype. In the hearts of HKO mice, unfolded protein response, EIF2 signaling, NRF2 signaling, prolactin signaling, β-adrenergic signaling, NFAT-induced immune response, and angiogenesis were downregulated, while necroptosis, fatty acid oxidation, glycolysis, and hypoxia signaling were upregulated.
These results demonstrate that miR-320a/b-mediated PERK suppression plays a key role in pathophysiology of PPCM. MiR-320a/b could serve as a biomarker and therapeutic target for PPCM with PE.
|
