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- Cerón-Pisa, Noemi, et al.
(författare)
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Hsa-Mir-320c, Hsa-Mir-200c-3p, and Hsa-Mir-449c-5p as Potential Specific miRNA Biomarkers of COPD : A Pilot Study
- 2022
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Ingår i: Pathophysiology. - : MDPI. - 0928-4680 .- 1873-149X. ; 29:2, s. 143-157
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease commonly induced by cigarette smoke. The expression of miRNAs can be altered in patients with COPD and could be used as a biomarker. We aimed to identify a panel of miRNAs in bron-choalveolar lavage (BAL) to differentiate COPD patients from smokers and non-smokers with normal lung function. Accordingly, forty-five subjects classified as COPD, smokers, and non-smokers (n = 15 per group) underwent clinical, functional characterization and bronchoscopy with BAL. The mean age of the studied population was 61.61 ± 12.95 years, BMI 25.72 ± 3.82 Kg/m2, FEV1/FVC 68.37 ± 12.00%, and FEV1 80.07 ± 23.63% predicted. According to microarray analysis, three miRNAs of the most upregulated were chosen: miR-320c, miR-200c-3p, and miR-449c-5p. These miRNAs were validated by qPCR and were shown to be differently expressed in COPD patients. ROC analysis showed that these three miRNAs together had an area under the curve of 0.89 in differentiating COPD from controls. Moreover, in silico analysis of candidate miRNAs by DIANA-miRPath showed potential involvement in the EGFR and Hippo pathways. These results suggest a specific 3-miRNA signature that could be potentially used as a biomarker to distinguish COPD patients from smokers and non-smoker subjects.
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| 2. |
- Medina-Dols, Aina, et al.
(författare)
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Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis
- 2024
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Ingår i: Cell Death Discovery. - : Springer Nature. - 2058-7716. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient's blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) <= 2), compared to those patients with marked disability (mRS = 4-5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1 alpha also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ss, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, beta-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery.
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