Abstract
Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling, which exists in both pulmonary arteries and pulmonary veins. Pulmonary vascular remodeling stems from excessive proliferation of pulmonary vascular myocytes. Platelet-derived growth factor-BB (PDGF-BB) is a vital vascular regulator whose level increases in PH human lungs. Although the mechanisms by which pulmonary arterial smooth muscle cells respond to PDGF-BB have been studied extensively, the effects of PDGF-BB on pulmonary venous smooth muscle cells (PVSMCs) remain unknown. We herein examined the involvement of calcium sensing receptor (CaSR) in PDGF-BB-induced PVSMCs proliferation under hypoxic conditions. In PVSMCs isolated from rat intrapulmonary veins, PDGF-BB increased the cell number and DNA synthesis under normoxic and hypoxic conditions, which was accompanied by upregulated CaSR expression. The influences of PDGF-BB on proliferation and CaSR expression in hypoxic PVSMCs were greater than that in normoxic PVSMCs. In hypoxic PVSMCs superfused with Ca2+-free solution, restoration of extracellular Ca2+ induced an increase of [Ca2+]i, which was significantly smaller than that in PDGF-BB-treated hypoxic PVSMCs. The positive CaSR modulator spermine enhanced, whereas the negative CaSR modulator NPS2143 attenuated, the extracellular Ca2+-induced [Ca2+]i increase in PDGF-BB-treated hypoxic PVSMCs. Furthermore, the spermine enhanced, whereas the NPS2143 inhibited, PDGF-BB-induced proliferation in hypoxic PVSMCs. Silencing CaSR with siRNA attenuated the extracellular Ca2+-induced [Ca2+]i increase in PDGF-BB-treated hypoxic PVSMCs and inhibited PDGF-BB-induced proliferation in hypoxic PVSMCs. In conclusion, these results demonstrated that CaSR mediating PDGF-BB-induced excessive PVSMCs proliferation is an important mechanism involved in the initiation and progression of PVSMCs proliferation under hypoxic conditions.
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18 September 2021
A Correction to this paper has been published: https://doi.org/10.1007/s10616-021-00488-x
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Acknowledgements
This work was supported by the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01S155), the Natural Science Foundation of Guangdong Province (2114050001676, 2017A030313683, 2017A030310419), the National key Research and Development program of China (2016YFC1304100, 2016YFC1304104, 2018YFC1311600), the National Natural Science Foundation of China (81570045), the Science and technology program of Guangzhou (201504010018), a Training Program for Academic Backbone of High Level Universities of Guangzhou Medical University (2017210) and a Grant of the First Affiliated Hospital of Guangzhou Medical University (201619). Dr. Peng was supported by the Scholarship of Guangzhou Medical University.
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Liu, R., Xu, J., Jiang, Y. et al. Platelet-derived growth factor-BB induces pulmonary venous smooth muscle cells proliferation by upregulating calcium sensing receptor under hypoxic conditions. Cytotechnology 73, 189–201 (2021). https://doi.org/10.1007/s10616-021-00456-5
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DOI: https://doi.org/10.1007/s10616-021-00456-5