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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
468
CircDiaph3 influences PASMC apoptosis by regulating PI3K/AKT/mTOR pathway through IGF1R
Ge Liu1, Shengqiang Zhang1, Shaofeng Yang1
1Department of Cardiac Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui People's Republic of China.
3 Biotech
|September 14, 2023
Summary
Circular RNA circDiaph3 promotes pulmonary artery smooth muscle cell proliferation and migration, contributing to pulmonary hypertension. Inhibiting circDiaph3 may offer a novel therapeutic strategy for this condition.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- RNA Biology
Background:
- Pulmonary hypertension (PH) pathogenesis remains unclear.
- Pulmonary artery smooth muscle cell (PASMC) proliferation is a key feature of PH.
- Circular RNAs (circRNAs) are emerging as critical regulators in cardiovascular diseases.
Purpose of the Study:
- To investigate the role of circDiaph3 in PH.
- To elucidate the molecular mechanisms underlying circDiaph3's function in PASMCs.
- To assess the therapeutic potential of circDiaph3 inhibition in a PH model.
Main Methods:
- Real-time quantitative PCR to analyze circDiaph3 expression in patient samples.
- Establishment of a rat model of hypoxic pulmonary arterial hypertension (PAH).
- Small interfering RNA (siRNA)-mediated knockdown of circDiaph3 in rat PASMCs and in vivo studies.
Main Results:
- CircDiaph3 was overexpressed in PH patients.
- CircDiaph3 knockdown downregulated PI3K/AKT/mTOR and IGF1R signaling pathways and smooth muscle cell markers (α-SMA, Vcam1).
- Overexpression of IGF1R rescued these effects, promoting proliferation and reducing apoptosis in PASMCs. In vivo inhibition of circDiaph3 ameliorated PAH in rats.
Conclusions:
- CircDiaph3 regulates PASMC proliferation and apoptosis via the PI3K/AKT/mTOR/IGF1R signaling axis.
- Excessive PASMC proliferation contributes to pulmonary artery lumen narrowing and PH.
- CircDiaph3 represents a potential therapeutic target for pulmonary hypertension.
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