Regulation of TGF‑β1 on PI3KC3 and its role in hypertension‑induced vascular injuries

Abstract

The aim of the present study was to investigate the expression and role of transforming growth factor (TGF)-β1/phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3) in the peripheral blood in patients with hypertension. A total of 28 patients with primary hypertension and 20 healthy control subjects were included. Peripheral blood samples were collected. The mRNA and protein expression levels were detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Cell counting kit-8 assay, Transwell chamber assay and flow cytometry were performed to detect the cell proliferation, migration ability and cellular apoptosis, respectively. Laser scanning confocal microscopy was used to detect the intracellular autophagosomes. The expression of TGF-β1 was significantly elevated, whereas the expression of PI3KC3 was significantly downregulated in the patients with hypertension compared with controls. There was negative correlation between the TGF-β1 and PI3KC3 expression. Following treatment with TGF-β1, the protein expression of PI3KC3 was significantly decreased in human umbilical vein endothelial cells (HUVECs), and the autophagic activity was significantly decreased. Furthermore, following the treatment of TGF-β1 the proliferation of HUVECs was significantly reduced in the HUVECs, the hypoxia-induced apoptosis rates were significantly elevated and the number of penetrating cells were significantly declined (indicating declined migration ability). However, the overexpression of PI3KC3 significantly ameliorated the proliferation, migration ability and hypoxia tolerance of TGF-β1-treated HUVECs. In conclusion, the present results indicated that TGF-β1 expression was elevated in the peripheral blood in hypertensive patients and negatively correlated with the PI3KC3 expression; and that TGF-β1 regulates the PI3KC3 signaling pathway to inhibit the autophagic activity of vascular endothelial cells, and regulate the cell proliferation, migration and anti-apoptosis ability, thus aggregating the endothelial cell injuries in hypertension. The results of the current study revealed a novel mechanism of TGF-β1 in the regulation of endothelial cell injury in hypertension, which may provide a potential target for disease therapy.

Foxf2 and Smad6 co‐regulation of collagen 5A2 transcription is involved in the pathogenesis of intrauterine adhesion

“…However, it had been reported that TGF-β1 inhibited cell proliferation in many studies. [44][45][46] TGF-β1 may have a dual role on cell proliferation, and there had also many studies reported that TGF-β1 promotes proliferation. 47,48 The TGF-β signalling pathway is initiated when an activated TGF-β ligand binds to its membrane receptors, TGF-β type II receptor (TβRII) and TGF-β type I receptor (TβRI).…”

“…In the present study, TGF‐β1 induced HESC proliferation and promoted cell cycle progression from G0/G1 to S phase (Figure A,B). However, it had been reported that TGF‐β1 inhibited cell proliferation in many studies . TGF‐β1 may have a dual role on cell proliferation, and there had also many studies reported that TGF‐β1 promotes proliferation …”

Automated high-throughput live cell monitoring of endothelial cell migration

“…The role of TGF-β in the context of endothelial cells seems to be contradictory in literature. On the one hand, a reduction in trans-well migration of HUVECs caused by TGF-β through phosphatidylinositol 3-kinase catalytic subunit type 3 has recently been described (Zhang et al, 2019b). In line, medium transferred from TGF-β -treated dental pulp stem cells to HUVECs reduced their migratory activity compared to medium transferred from respective control cells (Zhang et al, 2021).…”