Mir-455-3p-1 represses FGF7 expression to inhibit pulmonary arterial hypertension through inhibiting the RAS/ERK signaling pathway

Zhou, Chengke; Chen, Yu; Kang, Wanying; Lv, Hong; Fang, Zhongrong; Yan, Fuxia; Li, Lihuan; Zhang, Weili; Shi, Jia

doi:10.1016/j.yjmcc.2019.03.002

Cited by 31 publications

(24 citation statements)

References 36 publications

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“…The mRNA level of FGF-7 was upregulated in tissues obtained from PAH patients and in PAH-PASMCs [88]. miR-455-3p-1 alleviated PAH by regulating FGF7 and RAS/ERK signaling, respectively [88]. In a recent study, there were decreased levels of miR-181a-5p and miR-181b-5p, whereas the protein level of endocan was elevated in monocrotaline-induced PAH in a time-dependent manner [89].…”

Section: Pahmentioning

confidence: 99%

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miRNAs in Lung Development and Diseases

Boateng

Krauss‐Etschmann

2020

IJMS

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The development of the lung involves a diverse group of molecules that regulate cellular processes, organ formation, and maturation. The various stages of lung development are marked by accumulation of small RNAs that promote or repress underlying mechanisms, depending on the physiological environment in utero and postnatally. To some extent, the pathogenesis of various lung diseases is regulated by small RNAs. In this review, we discussed miRNAs regulation of lung development and diseases, that is, COPD, asthma, pulmonary fibrosis, and pulmonary arterial hypertension, and also highlighted possible connotations for human lung health.After fertilization in the mouse, total miRNA in the two-cell-stage embryo was demonstrated to be significantly lower than the levels in one-cell zygote [15]. Notably, total miRNA in the four-cell-stage embryo was higher than the levels in the two-cell-stage embryo [15]. In the early mouse embryo, miR-127 was upregulated at E6.5 and E7.5 [16]. Overexpression of miR-127 in mouse embryonic stem cells, which differentiated into embryoid bodies, increased the mRNA levels of Gsc, Foxa2, and Brachyury (mesendoderm markers), but elicited no change in Pax6 and Otx2 (ectoderm markers) three days after transfection. Inhibition of miR-127 showed opposite regulation of Gsc, Foxa2, and Brachyury. miR-127, moreover, was suggested to control mesendoderm differentiation [16]. miR-326 regulated sonic hedgehog signaling by targeting Smo and Gli2 [17]. The inhibition of smoothened in cultured explanted E12 mouse lung resulted in the expansion of distal epithelium, and disruption of normal branching pattern and mesenchymal integrity [17]. Another study described the functional role of miR-142-3p in the mouse embryonic lung mesenchyme. The miRNA was shown to regulate adenomatous polyposis coli to further modulate Wnt signaling [18]. Taken together, miR-142-3p regulated the proliferation and differentiation of mesenchymal progenitors in the mouse embryonic lung [18].In the developing mouse lung, the level of miR-17 was stable (E11.5-E16.5), predominantly at the pseudoglandular stage, with higher epithelial levels at E12.5 [19]. Simultaneous knockdown of miR-17 and its paralogs, miR-20a and miR-106b, for 72 h in epithelial lung explants altered branching, even in FGF10-treated condition [19]. In the human fetal lung, miR-449a was upregulated at 18-20 weeks (canalicular stage), and in the mouse embryonic lung, miR-449a level was increased from E15.5 to E18.5 [20]. The inhibition of miR-449a in E16.5 mouse lung culture (end of pseudoglandular stage) increased the mRNA levels of Mycn and Sox9, and the protein levels of Ki-67 and SOX9 particularly in the distal epithelial region [20].Knockout of miR-26a-1/miR-26a-2 in the mouse promoted the formation of dilated lumens and aerated regions at the beginning of the canalicular stage (E16.5) of lung development [21]. Results at the saccular stage (E18.5) also indicated large lamellar bodies, and increased SP-A, SP-B, and SP-C protein levels in miR-26a knockout mice....

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Section: Pahmentioning

confidence: 99%

“…It was further explained that miR-205-5p regulated MICAL2, a protein that proliferated hPASMCs via the activation of ERK1/2 signaling [87]. The mRNA level of FGF-7 was upregulated in tissues obtained from PAH patients and in PAH-PASMCs [88]. miR-455-3p-1 alleviated PAH by regulating FGF7 and RAS/ERK signaling, respectively [88].…”

Section: Pahmentioning

confidence: 99%

miRNAs in Lung Development and Diseases

Boateng

Krauss‐Etschmann

2020

IJMS

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“…The following genes showed similar expression patterns in both models: Pah , Fgf7 , Sptssb , Nd6 , Axdnd1 . Here, Pah 4 , 34 and Fgf7 33 have been previously implicated in hypertension, therefore further analysis of Sptssb , Nd6 , and Axdnd1 may help elucidate whether these genes contribute to development of hypertension. In fact, a full whole transcriptome profiling of the SHR adrenals will greatly contribute to this type of analysis.…”

Section: Discussionmentioning

confidence: 87%

“…1 e,f respectively, ranked based on fold change. Some of the DEGs have been previously associated with the development of hypertension, including Slc9A3 31 (solute carrier family 9 member A3; fold change = 4.55), Hpgd 32 (hydroxyprostaglandin dehydrogenase; fold change = 2.56), Pah 7 , 30 (phenylalanine hydroxylase; fold change = 2.10), Fgf7 33 (fibroblast growth factor 7; fold change = 2.05) and Cyp2e1 34 (cytochrome p450, family 2, subfamily e1; fold change = − 2.03) 7 , 34 , 35 . However, the majority of top dysregulated genes are currently not implicated in the development of hypertension.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, Pah has been recently identified as an adrenal stress sensitive gene and its expression is upregulated in adrenal glands of male rats exposed to chronic stress 56 . Fgf7 is another robustly upregulated DEG which has been linked to hypertension 33 . Repressing Fgf7 expression with mir-455-3p-1 inhibits pulmonary arterial hypertension by limiting RAS/ERK intracellular signaling.…”

Section: Discussionmentioning

confidence: 99%

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Whole transcriptome analysis of adrenal glands from prenatal glucocorticoid programmed hypertensive rodents

Tharmalingam

Khurana

Murray

et al. 2020

Sci Rep

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Prenatal glucocorticoid exposure is associated with the development of hypertension in adults. We have previously demonstrated that antenatal dexamethosone (DEX) administration in Wistar-Kyoto dams results in offspring with increased blood pressure coupled with elevated plasma epinephrine levels. In order to elucidate the molecular mechanisms responsible for prenatal DEX-mediated programming of hypertension, a whole-transcriptome analysis was performed on DEX programmed WKY male adrenal glands using the Rat Gene 2.0 microarray. Differential gene expression (DEG) analysis of DEX-exposed offspring compared with saline-treated controls revealed 142 significant DEGs (109 upregulated and 33 downregulated genes). DEG pathway enrichment analysis demonstrated that genes involved in circadian rhythm signaling were most robustly dysregulated. RT-qPCR analysis confirmed the increased expression of circadian genes Bmal1 and Npas2, while Per2, Per3, Cry2 and Bhlhe41 were significantly downregulated. In contrast, gene expression profiling of Spontaneously Hypertensive (SHR) rats, a genetic model of hypertension, demonstrated decreased expression of Bmal1 and Npas2, while Per1, Per2, Per3, Cry1, Cry2, Bhlhe41 and Csnk1D were all upregulated compared to naïve WKY controls. Taken together, this study establishes that glucocorticoid programmed adrenals have impaired circadian signaling and that changes in adrenal circadian rhythm may be an underlying molecular mechanism responsible for the development of hypertension.

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Single‐cell RNA‐seq reveals novel interaction between muscle satellite cells and fibro‐adipogenic progenitors mediated with FGF7 signalling

Ma,

Meng,

et al. 2024

J cachexia sarcopenia muscle

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BackgroundMuscle satellite cells (MuSCs) exert essential roles in skeletal muscle adaptation to growth, injury and ageing, and their functions are extensively modulated by microenvironmental factors. However, the current knowledge about the interaction of MuSCs with niche cells is quite limited.MethodsA 10× single‐cell RNA sequencing (scRNA‐seq) was performed on porcine longissimus dorsi and soleus (SOL) muscles to generate a single‐cell transcriptomic dataset of myogenic cells and other cell types. Sophisticated bioinformatic analyses, including unsupervised clustering analysis, marker gene, gene set variation analysis (GSVA), AUCell, pseudotime analysis and RNA velocity analysis, were performed to explore the heterogeneity of myogenic cells. CellChat analysis was used to demonstrate cell–cell communications across myogenic cell subpopulations and niche cells, especially fibro‐adipogenic progenitors (FAPs). Integrated analysis with human and mice datasets was performed to verify the expression of FGF7 across diverse species. The role of FGF7 on MuSC proliferation was evaluated through administering recombinant FGF7 to porcine MuSCs, C2C12, cardiotoxin (CTX)‐injured muscle and d‐galactose ( d‐gal)‐induced ageing model.ResultsScRNA‐seq totally figured out five cell types including myo‐lineage cells and FAPs, and myo‐lineage cells were further classified into six subpopulations, termed as RCN3+, S100A4+, ID3+, cycling (MKI67+), MYF6+ and MYMK+ satellite cells, respectively. There was a higher proportion of cycling and MYF6+ cells in the SOL population. CellChat analysis uncovered a particular impact of FAPs on myogenic cells mediated by FGF7, which was relatively highly expressed in SOL samples. Administration of FGF7 (10 ng/mL) significantly increased the proportion of EdU+ porcine MuSCs and C2C12 by 4.03 ± 0.81% (P < 0.01) and 6.87 ± 2.17% (P < 0.05), respectively, and knockdown of FGFR2 dramatically abolished the pro‐proliferating effects (P < 0.05). In CTX‐injured muscle, FGF7 significantly increased the ratio of EdU+/Pax7+ cells by 15.68 ± 5.45% (P < 0.05) and elevated the number of eMyHC+ regenerating myofibres by 19.7 ± 4.25% (P < 0.01). Under d‐gal stimuli, FGF7 significantly reduced γH2AX+ cells by 17.19 ± 3.05% (P < 0.01) in porcine MuSCs, induced EdU+ cells by 4.34 ± 1.54% (P < 0.05) in C2C12, and restored myofibre size loss and running exhaustion in vivo (all P < 0.05).ConclusionsOur scRNA‐seq reveals a novel interaction between muscle FAPs and satellite cells mediated by FGF7–FGFR2. Exogenous FGF7 augments the proliferation of satellite cells and thus benefits muscle regeneration and counteracts age‐related myopathy.

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Mir-455-3p-1 represses FGF7 expression to inhibit pulmonary arterial hypertension through inhibiting the RAS/ERK signaling pathway

Cited by 31 publications

References 36 publications

miRNAs in Lung Development and Diseases

miRNAs in Lung Development and Diseases

Whole transcriptome analysis of adrenal glands from prenatal glucocorticoid programmed hypertensive rodents

Single‐cell RNA‐seq reveals novel interaction between muscle satellite cells and fibro‐adipogenic progenitors mediated with FGF7 signalling

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