MiR‐195 promotes abdominal aortic aneurysm media remodeling by targeting Smad3

Liu, Bing; Che, Jianbo; Zhao, Hui; Zhang, Zhi; Shi, Gongning

doi:10.1111/1755-5922.12286

Cited by 21 publications

(16 citation statements)

References 35 publications

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“…From the screening stage, 10 miRNAs (miR-27b-3p [MIMAT0000419], miR-152-3p [MIMAT0000438], miR-7-1-3p [MIMAT0004553], miR-375 [MIMAT0000728], miR-103a-3p [MIMAT0000101], miR-144-3p [MIMAT0000436], miR-146a-5p [MIMAT0000449], miR-1260a [MIMAT0005911], miR-221-3p [MIMAT0000278], and miR-99a-5p [MIMAT0000097]) were selected as dysregulated in AAA plasma. Thus, they were quantified in the whole plasma sample set (N = 57), together with miR-195-5p [MIMAT0000461] because of its relation to AAA in previous literature [ 20 , 30 , 63 ]. miR-191-5 [MIMAT0000440] was used as normalizer.…”

Section: Methodsmentioning

confidence: 99%

Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients

Plana

Gálvez

Medina

et al. 2020

IJMS

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microRNAs (miRNAs) are small RNAs that regulate different biological processes. Our objective was to identify miRNAs dysregulated in plasma and tissue of patients with abdominal aortic aneurysm (AAA) and explore new potential targets involved in AAA. Fifty-seven subjects were recruited for a plasma study (30 AAA patients, 16 healthy volunteers and 11 patients with atherosclerosis). The expression level of 179 miRNAs was screened in plasma from a subset of samples, and dysregulated miRNAs were validated in the entire study population. Dysregulated miRNAs were also quantified in aortic tissue of 21 AAA patients and 8 organ donors. Applying a gene set enrichment analysis, an interaction map of dysregulated miRNAs and their targets was built, and selected targets were quantified in tissue samples. miR-27b-3p and miR-221-3p were overexpressed in plasma of AAA patients compared with healthy controls, 1.6 times and 1.9 times, respectively. In AAA tissue, six miRNAs (miR-1, miR-27b-3p, miR-29b-3p, miR-133a-3p, miR-133b, and miR-195-5p) were underexpressed from 1.6 to 4.8 times and four miRNAs (miR-146a-5p, miR-21-5p, miR-144-3p, and miR-103a-3p) were overexpressed from 1.3 to 7.2 times. Thrombospondin-2, a target of miR-195-5p, was increased in AAA tissue and negatively correlated with the expression of miR-195-5p, suggesting their involvement in a common regulatory mechanism.

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Section: Methodsmentioning

confidence: 99%

Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients

Plana

Gálvez

Medina

et al. 2020

IJMS

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“…Second, it can reduce inflammation by directly blocking the NF- κ B pathway, including IKK α and phosphorylated I κ Bs ( Yu et al, 2018 ). Its ability to block the NF- κ B pathway has been harnessed to inhibit the development of abdominal aortic aneurysm ( Liang et al, 2017 ) and chronic pulmonary obstructive disease (COPD) ( Li et al, 2020 ). Third, miR-195-5p has been found to inhibit the expression of pro-apoptotic protein Bax and active caspase-3 through suppressing IKK α /NF- κ B pathway and alleviate oxygen-glucose deprivation/reperfusion-induced cell apoptosis ( Yang, Cao & Zhang, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of and mechanisms underlying the effect of miR-195-5p on subarachnoid hemorrhage-induced vasospasm and brain injury in rats

Tsai

Chang

Lin

et al. 2021

PeerJ

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Objectives There is much evidence suggesting that inflammation contributes majorly to subarachnoid hemorrhage (SAH)-induced cerebral vasospasm and brain injury. miRNAs have been found to modulate inflammation in several neurological disorders. This study investigated the effect of miR-195-5p on SAH-induced vasospasm and early brain injury in experimental rats. Methods Ninety-six Sprague-Dawley male rats were randomly and evenly divided into a control group (no SAH, sham surgery), a SAH only group, a SAH + NC-mimic group, and a SAH + miR-195-5p group. SAH was induced using a single injection of blood into the cisterna magna. Suspensions containing NC-mimic and miR-195-5p were intravenously injected into rat tail 30 mins after SAH was induced. We determined degree of vasospasm by averaging areas of cross-sections the basilar artery 24h after SAH. We measured basilar artery endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κ B), phosphorylated NF-κ B (p-NF-κ B), inhibitor of NF-κ B (Iκ Bα) and phosphorylated-Iκ Bα (p-Iκ Bα). Cell death assay was used to quantify the DNA fragmentation, an indicator of apoptotic cell death, in the cortex, hippocampus, and dentate gyrus. Tumor necrosis factor alpha (TNF-α) levels were measured using sample protein obtained from the cerebral cortex, hippocampus and dentate gyrus. Results Prior to fixation by perfusion, there were no significant physiological differences among the control and treatment groups. SAH successfully induced vasospasm and early brain injury. MiR-195-5p attenuated vasospasam-induced changes in morphology, reversed SAH-induced elevation of iNOS, p-NF-κ B, NF-κ B, and p-Iκ Bα and reversed SAH-induced suppression of eNOS in the basilar artery. Cell death assay revealed that MiR-195-5p significantly decreased SAH-induced DNA fragmentation (apoptosis) and restored TNF-α level in the dentate gyrus. Conclusion In conclusion, MiRNA-195-5p attenuated SAH-induced vasospasm by up-regulating eNOS, down-regulating iNOS and inhibiting the NF-κ B signaling pathway. It also protected neurons by decreasing SAH-induced apoptosis-related cytokine TNF-α expression in the dentate gyrus. Further study is needed to elucidate the detail mechanism underlying miR-195-5p effect on SAH-induced vasospasm and cerebral injury. We believe that MiR-195-5p can potentially be used to manage SAH-induced cerebral vasospasm and brain injury.

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“…SMAD2 mainly promotes growth and differentiation of hepatocytes, whereas SMAD3 promotes morphological and functional maturation of hepatic stellate cells [21,22]. In addition, SMAD3 is implicated in abdominal aortic aneurysm, osteoarthritis, mesenchymal cell transition, and cardiac fibrosis [23][24][25][26]. The role of SMAD3 in different cancer types has not been fully explored.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of small mother against decapentaplegic expression in human gastric cancer

et al. 2021

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Gastric cancer is the fifth most common malignancy in the world with alow 5-year survival rate. To date, no study has investigated the prognostic role of the small mother against decapentaplegic (SMAD) in gastric cancer. The association of SMADs with overall survival (OS) of gastric cancer was analyzed on the online Kaplan-Meier (KM) plotter database. Clinical data such as stage, differentiation, gender, treatment, and Her2 mutation status of gastric cancer patients were analyzed. The (E)-SIS3 was used to inhibit SMAD3 expression in gastric cancer cells, and the effects of SMAD3 on gastric cancer cells were analyzed via real-time cellular analysis (RTCA), flow cytometry, colony formation, and immunofluorescence assay. The results showed that the high expression of three members of SMADs (SMAD1, SMAD2, SMAD4) was correlated with afavorable OS of gastric cancer patients. Meanwhile, SMAD3 expression level indicated highly differentiated cancer. We also observed that surgical treatment was associated with high expression level of SMAD1 and SMAD2. Besides, the effect of Her2 on gastric cancer was not noticeable. Moreover, (E)-SIS3 pharmacological assay revealed that inhibition of expression of SMAD3 suppressed the proliferation and migration ability of gastric cancer cells via inducing apoptosis. Collectively, these results demonstrate that the high expression level of three members of SMADs (SMAD1, SMAD2, and SMAD4) is significantly correlated with favorable OS of gastric cancer patients, which is opposite to SMAD3. Thus, SMADs regulate the differentiation of cancer and can be used to guide treatment decisions.

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MiR‐195 promotes abdominal aortic aneurysm media remodeling by targeting Smad3

Abstract: MiR-195 promotes media remodeling by targeting Smad3 in AAA progression. This study suggests that miR-195 contributes to the pathogenesis of AAA and reveals a new targeted therapy strategy for AAA patients.

Cited by 21 publications

References 35 publications

Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients

Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients

Therapeutic effect of and mechanisms underlying the effect of miR-195-5p on subarachnoid hemorrhage-induced vasospasm and brain injury in rats

Prognostic value of small mother against decapentaplegic expression in human gastric cancer

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