Galectin‐3 mediates pulmonary vascular endothelial cell dynamics via TRPC1/4 under acute hypoxia

Abstract

Galectin-3 (Gal-3) has been implicated in various biological functions, yet little is known about its role in regulating the dynamics of pulmonary vascular endothelial cells. Gal-3 was shown to be increased in hypoxic model rats by sequencing analysis. We exposed pulmonary vessel endothelial cells (PVECs) to hypoxia or Gal-3 stimulation, following which cell apoptosis and autophagy were measured with the relevant methods. The results demonstrated that hypoxia elevated nuclear factor-κB (NF-κB) activity and Gal-3 expression. Gla-3 decreased the expression of Bcl-2, Alix, Beclin-1, Atg5, and LC3A/B. The messenger RNA and protein levels of transient receptor potential channel 1/4 (TRPC1/4) and calpain were reduced after Gal-3 treatment. Gal-3 also activated protein kinase B/glycogen synthase kinase-3 β/mammalian target of rapamycin signaling pathways in PVECs. These results suggest that a hypoxia-mediated increase in Gal-3 promotes apoptosis and inhibits autophagy by inhibiting the TRPC1/4 pathway and activating the protein kinase B/glycogen synthase kinase-3 β/mammalian target of rapamycin signaling pathway in PVECs. Furthermore, these results may provide us with a new direction to explore the pathogenesis of pulmonary artery hypertension. K E Y W O R D S apoptosis, autophagy, calpain, galectin-3, TRPCs

Supplementation with Tex261 provides a possible preventive treatment for hypoxic pulmonary artery hypertension

“…Our results showed that hypoxia induced Akt inactivation, but treatment with Akt agonists or blockers reversed the change in Sec23 after Ndrg1 interference, indicating that Ndrg1 regulates Sec23 through Akt pathways. Moreover, Akt pathways were reported to play a role in PAH (de Jesus Perez et al, 2014;Li et al, 2020), and our results also showed that the pathways were involved in PASMC proliferation after hypoxia. Furthermore, we observed that Ndrg1 was enhanced and mainly expressed in the cytoplasm, while Sec23 was weakened, mainly in the nucleus after hypoxia stimulation through immunofluorescence, indicating that there were differences in expression in time and space between the two proteins.…”

Transgenerational inheritance of promoter methylation changes in extrauterine growth restriction-induced pulmonary arterial pressure disorders

“…Features including stress to endothelial cells and their corresponding apoptosis are noticed in PAH individuals (4). As known studies and our pilot observation have shown, pulmonary vascular endothelial cell (PVEC) injury is one of the pathogeneses of PAH (e.g., decreased Notch1 in PVECs) (5)(6)(7).…”

Galectin-3: a key player in microglia-mediated neuroinflammation and Alzheimer's disease

“…Studies have shown that Gal-3 activates the Wnt/βcatenin signalling pathway and then regulates cell proliferation, invasion, and migration [43,44]. The interaction of Gal-3 and B-cell lymphoma-2 (Bcl-2) generates cell apoptotic events and restrains autophagy via the (TRPC1/4) signalling pathway and Akt phosphorylation of glycogen synthase kinase-3β (GSK-3β) [45,46]. Gal-3 also modulates cell apoptosis by interacting with synexin [47], nucling [48] and CD95 (APO-1/Fas) [49].…”