MicroRNA-29b regulates pyroptosis involving calcific aortic valve disease through the STAT3/SOCS1 pathway

Background: CAVD (calcific aortic valve disease) involves an inflammatory response similar to pyroptosis; therefore, we speculated that the progression of pyroptosis might be involved in the pathogenesis of CAVD.Methods: We first investigated the expression of pyroptosis related genes in human CAVD, non-CAVD control and AS (calcific aortic stenosis) tissues. We further confirmed these genes by using CAVD cell and mouse models.Finally, we explored the functional molecular mechanism in the cell model.Results: Our recent studies found that miR-29b plays an important role in CAVD, and we wanted to further address whether miR-29b is a key factor in the progression of pyroptosis related to CAVD. In this study, we found NLRP3 was highly expressed in CAVD patients and models. In contrast, SOCS1, a suppressor of NLRP3, showed reduced expression in CAVD. Furthermore, we found that ASC, Caspase-1, IL-1 & beta;, Cleaved IL-18 and p-JAK2 were all upregulated in the tissues of CAVD patients, suggesting the likelihood of activation of the inflammasome. Then, we found that miR-29b participated in the NLRP3-regulated CAVD pathway through its target gene STAT3 (signal transducer and activator of transcription 3). Finally, we found that a miR-29b inhibitor could mitigate the increases in osteogenic differentiation and pyroptosis and that SOCS1 showed negative regulation of osteogenic differentiation and pyroptosis in CAVD.Conclusion: These findings suggested NLRP3 inflammasome-related genes are highly expressed in CAVD, and miR-29b reverses osteoblastic differentiation of aortic valve interstitial cells by regulating pyroptosis and inhibiting inflammation via the STAT3/SOCS1 pathway.

Automated summary

This study found that NLRP3-related genes are highly expressed in CAVD, while the expression of SOCS1 is reduced. MiR-29b participates in the NLRP3-regulated CAVD pathway and reverses osteoblastic differentiation of aortic valve interstitial cells by regulating pyroptosis and inhibiting inflammation via the STAT3/SOCS1 pathway. Furthermore, a miR-29b inhibitor can mitigate the increases in osteogenic differentiation and pyroptosis in CAVD.