{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:45:07Z","timestamp":1790675107984,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T00:00:00Z","timestamp":1617840000000},"content-version":"vor","delay-in-days":97,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004763","name":"Natural Science Foundation of Inner Mongolia Autonomous Region","doi-asserted-by":"publisher","award":["2018LH0823"],"award-info":[{"award-number":["2018LH0823"]}],"id":[{"id":"10.13039\/501100004763","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81460011"],"award-info":[{"award-number":["81460011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Previous studies have demonstrated the ubiquitin\u2010proteasome inhibitor bortezomib (BTZ) can effectively alleviate hypoxia\u2010induced pulmonary hypertension (HPH) by suppressing the intracellular calcium homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Further evaluation showed that the antiproliferation roles of BTZ are mainly mediated by inhibition of the intracellular calcium homeostasis. Caveolin\u20101 belongs to one of the key regulators of the intracellular calcium homeostasis in PASMCs, which can regulate the store\u2010operated calcium entry (SOCE). However, the effects of BTZ on Caveolin\u20101 remain unclear. <jats:italic>Methods<\/jats:italic>. Primarily cultured human PASMCs were used as the cell model. CCK\u20108 assay was performed to assess the PASMCs proliferation. Western blotting and real\u2010time qPCR were used to detect the mRNA and protein expressions. Fura\u20102\u2010based fluorescence imaging experiments were used to determine the intracellular calcium concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>). The protein synthesis inhibitor cycloheximide (CHX) was utilized to determine the protein degradation process. <jats:italic>Results<\/jats:italic>. Firstly, in cultured human PASMCs, treatment of BTZ for 24 or 60 hours significantly downregulates Caveolin\u20101 at both mRNA and protein levels. Secondly, in the presence CHX, BTZ treatment also leads to downregulated protein expression and fastened protein degradation of Caveolin\u20101, indicating that BTZ can promote the Caveolin\u20101 protein degradation, other than the BTZ on Caveolin\u20101 mRNA transcription. Then, BTZ significantly attenuates the hypoxia\u2010elevated baseline [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, SOCE, and cell proliferation. <jats:italic>Conclusion<\/jats:italic>. We firstly observed that the ubiquitin\u2010proteasome inhibitor BTZ can inhibit the Caveolin\u20101 expression at both mRNA transcription and protein degradation processes, providing new mechanistic basis of BTZ on PASMC proliferation.<\/jats:p>","DOI":"10.1155\/2021\/5551504","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T20:54:48Z","timestamp":1617915288000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bortezomib Inhibits Hypoxia\u2010Induced Proliferation by Suppressing Caveolin\u20101\/SOCE\/[Ca<sup>2+<\/sup>]<sub>i<\/sub> Signaling Axis in Human 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