Mir-573 regulates cell proliferation and apoptosis by targeting Bax in human degenerative disc cells following hyperbaric oxygen treatment

Abstract

Background MicroRNA (miRNA) plays a vital role in the intervertebral disc (IVD) degeneration. The expression level of miR-573 was downregulated whereas Bax was upregulated notably in human degenerative nucleus pulposus cells. In this study, we aimed to investigate the role of miR-573 in human degenerative nucleus pulposus (NP) cells following hyperbaric oxygen (HBO) treatment. Methods NP cells were separated from human degenerated IVD tissues. The control cells were maintained in 5% CO2/95% air and the hyperoxic cells were exposed to 100% O2 at 2.5 atmospheres absolute. MiRNA expression profiling was performed via microarray and confirmed by real-time PCR, and miRNA target genes were identified using bioinformatics and luciferase reporter assays. The mRNA and protein levels of Bax were measured. The proliferation of NPCs was detected using MTT assay. The protein expression levels of Bax, cleaved caspase 9, cleaved caspase 3, pro-caspase 9, and pro-caspase 3 were examined. Results Bioinformatics analysis indicated that the 3′ untranslated region (UTR) of the Bax mRNA contained the “seed-matched-sequence” for hsa-miR-573, which was validated via reporter assays. MiR-573 was induced by HBO and simultaneous suppression of Bax was observed in NP cells. Knockdown of miR-573 resulted in upregulation of Bax expression in HBO-treated cells. In addition, overexpression of miR-573 by HBO increased cell proliferation and coupled with inhibition of cell apoptosis. The cleavage of pro-caspase 9 and pro-caspase 3 was suppressed while the levels of cleaved caspase 9 and caspase 3 were decreased in HBO-treated cells. Transfection with anti-miR-573 partly suppressed the effects of HBO. Conclusion Mir-573 regulates cell proliferation and apoptosis by targeting Bax in human degenerative NP cells following HBO treatment.

HBO Alleviates Neural Stem Cell Pyroptosis via lncRNA-H19/miR-423-5p/NLRP3 Axis and Improves Neurogenesis after Oxygen Glucose Deprivation

“…It has been reported that HBO treatment induces lncRNA-MALAT1 to target miR-92a/KLF2 for angiogenesis after myocardial infarction [21]. HBO treatment suppressed the degeneration of nucleus pulposus cells via miR-107 and miR-573 [19,20]. In the current study, we found that HBO treatment suppressed the activation of NLRP3-dependent pyroptosis signaling in NSCs following OGD by downregulation of lncRNA-H19.…”

“…HBO treatment not only enhances the viability and survival of NSCs but also enhances NSC proliferation and differentiation into neurons after ischemic injury [16][17][18]. Recent studies have proven that HBO exerts therapeutic roles in various pathophysiologies of hypoxic/ischemic diseases by regulating noncoding RNA [19][20][21]. In this present study, an OGD exposure and HBO treatment model of NSCs in vitro was established with a purpose to investigate the effect and mechanism of HBO treatment on the presumed lncRNA-H19-associated pyroptosis of NSCs following OGD and clarify its influence on NSC proliferation and differentiation.…”

Hyperbaric Oxygen Therapy and Tissue Regeneration: A Literature Survey

“…Accordingly, the overexpression of miR-573 following HBO inhibited apoptosis and enhanced proliferation. As in the preceding study, transfection with an antagonist of miR-573 partly suppressed the effects of HBO [ 67 ].…”

Hyperbaric oxygen therapy for the treatment of hypoxic/ischemic injury upon perinatal asphyxia—are we there yet?

“…Importantly, miRNAs influencing the activity of the Wnt pathway, e.g., mir-128, mir-148, mir-151a, mir-181a, mir-181b, mir-374a, or mir-376c-3p, can also regulate apoptosis ( 55 , 58 , 67 ). Mir-573, upregulated after HBOT, was responsible for the repression of Bax mRNA, consequently cleaved forms of caspase-3 and caspase-9 were also decreased ( 74 ).…”