Dr. Hsieh, Patrick Ching-Ho
Distinguished Research Fellow
Division Chief
- 02-27899170 (Lab) (Room No: N417)
- 02-27858594 (Fax)
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Specialty:
- Stem cells and regenerative medicine
- Nanoscience and nanomedicine
- Translational Research
Education and Positions:
M.D. Kaohsiung Medical College
Ph.D. University of Washington, Seattle (Bioengineering)
Highlight Detail
MicroRNA let-7-TGFBR3 signalling regulates cardiomyocyte apoptosis after infarction
Dr. Hsieh, Patrick Ching-Ho
EBioMedicine, Aug 07, 2019Background
Myocardial infarction (MI) is a life-threatening disease, often leading to heart failure. Defining therapeutic targets at an early time point is important to prevent heart failure.
Methods
MicroRNA screening was performed at early time points after MI using paired samples isolated from the infarcted and remote myocardium of pigs. We also examined the microRNA expression in plasma of MI patients and pigs. For mechanistic studies, AAV9-mediated microRNA knockdown and overexpression were administrated in mice undergoing MI.
Findings
MicroRNAs let-7a and let-7f were significantly downregulated in the infarct area within 24 h post-MI in pigs. We also observed a reduction of let-7a and let-7f in plasma of MI patients and pigs. Inhibition of let-7 exacerbated cardiomyocyte apoptosis, induced a cardiac hypertrophic phenotype, and resulted in worsened left ventricular ejection fraction. In contrast, ectopic let-7 overexpression significantly reduced those phenotypes and improved heart function. We then identified TGFBR3 as a target of let-7, and found that induction of Tgfbr3 in cardiomyocytes caused apoptosis, likely through p38 MAPK activation. Finally, we showed that the plasma TGFBR3 level was elevated after MI in plasma of MI patients and pigs.
Interpretation
Together, we conclude that the let-7-Tgfbr3-p38 MAPK signalling plays an important role in cardiomyocyte apoptosis after MI. Furthermore, microRNA let-7 and Tgfbr3 may serve as therapeutic targets and biomarkers for myocardial damage.
Fund
Ministry of Science and Technology, National Health Research Institutes, Academia Sinica Program for Translational Innovation of Biopharmaceutical Development-Technology Supporting Platform Axis, Thematic Research Program and the Summit Research Program, Taiwan.