Mir-21 Mediates the Inhibitory Effect of Ang (1–7) on AngII-induced NLRP3 Inflammasome Activation by Targeting Spry1 in lung fibroblasts

Sun, Nana; Yu, Changhui; Pan, Miao; Zhang, Yue; Zheng, Bojun; Yang, Qianjie; Zheng, Zemao; Meng, Ying

doi:10.1038/s41598-017-13305-3

Cited by 48 publications

(32 citation statements)

References 44 publications

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“…Elevated miR-21 expression levels were reported to be associated with organ fibrosis, such as lung, kidney, liver, and heart via promoting fibroblast activation [12,16,39,40]. Several reports have shown the fibrogenic function of miR-21 in fibroblasts through modulation of its target genes, such as PDCD4, Smad7, PTEN, and Spry1 [12,15,26,27].…”

Section: Discussionmentioning

confidence: 99%

The association between microRNA-21 and hypertension-induced cardiac remodeling

et al. 2020

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Hypertension is a major public health problem among the aging population worldwide. It causes cardiac remodeling, including hypertrophy and interstitial fibrosis, which leads to development of hypertensive heart disease (HHD). Although microRNA-21 (miR-21) is associated with fibrogenesis in multiple organs, its contribution to cardiac remodeling in hypertension is poorly understood. Circulating miR-21 level was higher in patients with HHD than that in the control subjects. It also positively correlated with serum myocardial fibrotic markers. MiR-21 expression levels were significantly upregulated in the mice hearts after angiotensin II (Ang II) infusion or transverse aortic constriction (TAC) compared with control mice. Expression level of programmed cell death 4 (PDCD4), a main target of miR-21, was significantly decreased in Ang II infused mice and TAC mice compared with control mice. Expression levels of transcriptional activator protein 1 (AP-1) and transforming growth factor-β1 (TGF-β1), which were downstream targets of PDCD4, were increased in Ang II infused mice and TAC mice compared with control mice. In vitro, mirVana-miR-21-specific inhibitor attenuated Ang II-induced PDCD4 downregulation and contributed to subsequent deactivation of AP-1/TGF-β1 signaling pathway in neonatal rat cardiomyocytes. Thus, suppression of miR-21 prevents hypertrophic stimulation-induced cardiac remodeling by regulating PDCD4, AP-1, and TGF-β1 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

The association between microRNA-21 and hypertension-induced cardiac remodeling

et al. 2020

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“…Wang et al, 2008). In particular, activation of the ACE2/Ang(1-7) axis leads to inhibition of NLRP3 inflammasomes, associated with the downregulation of angiotensin II-induced mir-21 (Sun et al, 2017). It is possible that a similar pathway may be activated by SARS-CoV-2.…”

Section: The Nlrp3 Inflammasome and Its Role In Viral Infectionmentioning

confidence: 99%

The hidden role of NLRP3 inflammasome in obesity‐related COVID‐19 exacerbations: Lessons for drug repurposing

Bertocchi

Foglietta

Collotta

et al. 2020

British J Pharmacology

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COVID-19, the illness caused by SARS-CoV-2, has a wide-ranging clinical spectrum that, in the worst-case scenario, involves a rapid progression to severe acute respiratory syndrome and death. Epidemiological data show that obesity and diabetes are among the main risk factors associated with high morbidity and mortality. The increased susceptibility to SARS-CoV-2 infection documented in obesity-related metabolic derangements argues for initial defects in defence mechanisms, most likely due to an elevated systemic metabolic inflammation ("metaflammation"). The NLRP3 inflammasome is a master regulator of metaflammation and has a pivotal role in the pathophysiology of either obesity or diabetes. Here, we discuss the most recent findings suggesting contribution of NLRP3 inflammasome to the increase in complications in COVID-19 patients with diabesity. We also review current pharmacological strategies for COVID-19, focusing on treatments whose efficacy could be due, at least in part, to interference with the activation of the NLRP3 inflammasome.

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“…Further literature implicates ACE2 signaling in NLRP3 activation in multiple settings. AngII can induce NLRP3 inflammasome activation in renal tubular epithelial cells (23), AngII induces pulmonary fibrosis which is attenuated by ACE2 (24), and NLRP3 inflammasome activation drives Ang II-induced vascular smooth muscle cell (VSMC) proliferation and vascular remodeling and hypertension (25,26).…”

Section: Introductionmentioning

confidence: 99%

Targeting the NLRP3 Inflammasome in Severe COVID-19

2020

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the genus Betacoronavirus within the family Coronaviridae. It is an enveloped single-stranded positive-sense RNA virus. Since December of 2019, a global expansion of the infection has occurred with widespread dissemination of coronavirus disease 2019 (COVID-19). COVID-19 often manifests as only mild cold-like symptomatology, but severe disease with complications occurs in 15% of cases. Respiratory failure occurs in severe disease that can be accompanied by a systemic inflammatory reaction characterized by inflammatory cytokine release. In severe cases, fatality is caused by the rapid development of severe lung injury characteristic of acute respiratory distress syndrome (ARDS). Although ARDS is a complication of SARS-CoV-2 infection, it is not viral replication or infection that causes tissue injury; rather, it is the result of dysregulated hyperinflammation in response to viral infection. This pathology is characterized by intense, rapid stimulation of the innate immune response that triggers activation of the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathway and release of its products including the proinflammatory cytokines IL-6 and IL-1β. Here we review the literature that describes the pathogenesis of severe COVID-19 and NLRP3 activation and describe an important role in targeting this pathway for the treatment of severe COVID-19.

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Mir-21 Mediates the Inhibitory Effect of Ang (1–7) on AngII-induced NLRP3 Inflammasome Activation by Targeting Spry1 in lung fibroblasts

Cited by 48 publications

References 44 publications

The association between microRNA-21 and hypertension-induced cardiac remodeling

The association between microRNA-21 and hypertension-induced cardiac remodeling

The hidden role of NLRP3 inflammasome in obesity‐related COVID‐19 exacerbations: Lessons for drug repurposing

Targeting the NLRP3 Inflammasome in Severe COVID-19

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