MiR-21 Induced Angiogenesis through AKT and ERK Activation and HIF-1α Expression

Liu, Lingzhi; Li, Chong-Yong; Chen, Qi; Yi, Jing; Carpenter, Richard L.; Jiang, Yue; Kung, Hsiang‐Fu; Lai, Lihui; Jiang, Bing‐Hua

doi:10.1371/journal.pone.0019139

Cited by 433 publications

(383 citation statements)

References 48 publications

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“…This is not surprising, as several of the key molecular regulators of angiogenesis, such as VEGFs, are also common to lymphangiogenesis during inflammation (1). miR-21, which has been shown to be both anti-and proangiogenic (33,52), is significantly upregulated in LECs in response to TNF-␣ ( Table 1). Results of the latter study (52) are consistent with our findings that miR-21 mimics reduced tube formation in LECs (Fig.…”

Section: Mir-21 and The Mir-17-92 Clustermentioning

confidence: 99%

MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation

Chakraborty

Zawieja

Davis

et al. 2015

American Journal of Physiology-Cell Physiology

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Chakraborty S, Zawieja DC, Davis MJ, Muthuchamy M. MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation. Am J Physiol Cell Physiol 309: C680 -C692, 2015. First published September 9, 2015; doi:10.1152/ajpcell.00122.2015.-The lymphatics have emerged as critical players in the progression and resolution of inflammation. The goal of this study was to identify specific microRNAs (miRNAs) that regulate lymphatic inflammatory processes. Rat mesenteric lymphatic endothelial cells (LECs) were exposed to the proinflammatory cytokine tumor necrosis factor-␣ for 2, 24, and 96 h, and miRNA profiling was carried out by real-time PCR arrays. Our data demonstrate a specific set of miRNAs that are differentially expressed (Ͼ1.8-fold and/or P Ͻ 0.05) in LECs in response to tumor necrosis factor-␣ and are involved in inflammation, angiogenesis, endothelial-mesenchymal transition, and cell proliferation and senescence. We further characterized the expression of miRNA 9 (miR-9) that was induced in LECs and in inflamed rat mesenteric lymphatics. Our results showed that miR-9 overexpression significantly repressed NF-B expression and, thereby, suppressed inflammation but promoted LEC tube formation, as well as expression of the prolymphangiogenic molecules endothelial nitric oxide synthase and VEGF receptor type 3. LEC viability and proliferation and endothelial-mesenchymal transition were also significantly induced by miR-9. This study provides the first evidence of a distinct profile of miRNAs associated with LECs during inflammation. It also identifies the critical dual role of miR-9 in fine-tuning the balance between lymphatic inflammatory and lymphangiogenic pathways.

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Section: Mir-21 and The Mir-17-92 Clustermentioning

confidence: 99%

MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation

Chakraborty

Zawieja

Davis

et al. 2015

American Journal of Physiology-Cell Physiology

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“…This observation unveils a novel pathway Both AKT and ERK are downstream regulators of the miR-21/PTEN pathway. 46 It is also known that ENaC activity is regulated by a complex network of signaling pathways in addition to the AKT and ERK pathways. 50 We previously demonstrated that the AKT pathway mediated the LPSinduced decrease of cystic fibrosis transmembrane conductance regulator protein expression in primary ATII cells.…”

Section: Discussionmentioning

confidence: 99%

“…46 Therefore, we examined whether these signaling pathways were involved in the regulation of ENaC-γ protein expression after LPS treatment. First, we examined the phosphorylation of AKT and ERK in LPS-stimulated A549 cells.…”

Section: Lps Decreased Enac-γ Protein Expression In a Mir-21/ Pten Akmentioning

confidence: 99%

Lipoxin A4 activates alveolar epithelial sodium channel gamma via the microRNA-21/PTEN/AKT pathway in lipopolysaccharide-induced inflammatory lung injury

Cai

et al. 2015

Laboratory Investigation

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Lipoxin A 4 (LXA 4 ), as an endogenously produced lipid mediator, promotes the resolution of inflammation. Previously, we demonstrated that LXA 4 stimulated alveolar fluid clearance through alveolar epithelial sodium channel gamma (ENaC-γ). In this study, we sought to investigate the mechanisms of LXA 4 in modulation of ENaC-γ in lipopolysaccharide (LPS)-induced inflammatory lung injury. miR-21 was upregulated during an LPS challenge and downregulated by LXA 4 administration in vivo and in vitro. Serum miR-21 concentration was also elevated in acute respiratory distress syndrome patients as compared with healthy volunteers. LPS increased miR-21 expression by activation of activator protein 1 (AP-1). In A549 cells, miR-21 upregulated phosphorylation of AKT activation via inhibition of phosphatase and tensin homolog (PTEN), and therefore reduced the expression of ENaC-γ. In contrast, LXA 4 reversed LPS-inhibited ENaC-γ expression through inhibition of AP-1 and activation of PTEN. In addition, an miR-21 inhibitor mimicked the effects of LXA 4 ; overexpression of miR-21 abolished the protective effects of LXA 4 . Finally, both AKT and ERK inhibitors (LY294002 and UO126) blocked effects of LPS on the depression of ENaC-γ. However, LXA 4 only inhibited LPS-induced phosphorylation of AKT. In summary, LXA 4 activates ENaC-γ in part via the miR-21/PTEN/AKT signaling pathway.

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“…Many of the bovine miRNAs differentially expressed in large atretic follicles are reportedly involved in regulating the proliferation and survival of different cell types (miR-483, miR-150, miR-21, miR-409a, miR-31, miR-34b, miR-33a; Yamakuchi et al 2008, Bertero et al 2011, Liu et al 2011, Brabletz 2012, Cirera-Salinas et al 2012, Weng et al 2012 as well as immune cell activation (miR-150, miR-21, miR-31; Xiao et al 2007, Xue et al 2013, Das et al 2014, which is consistent with an active role of these miRNAs in follicular fate decisions. The involvement of miR-21 in the promotion of cell survival is well established, including in mouse granulosa cells during ovulation (Carletti et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Characterization of microRNAs differentially expressed during bovine follicle development

Sontakke¹,

Mohammed²,

McNeilly³

et al. 2014

Reproduction

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Several different miRNAs have been proposed to regulate ovarian follicle function; however, very limited information exists on the spatiotemporal patterns of miRNA expression during follicle development. The objective of this study was to identify, using microarray, miRNA profiles associated with growth and regression of dominant-size follicles in the bovine monovular ovary and to characterize their spatiotemporal distribution during development. The follicles were collected from abattoir ovaries and classified as small (4-8 mm) or large (12-17 mm); the latter were further classified as healthy or atretic based on estradiol and CYP19A1 levels. Six pools of small follicles and individual large healthy (nZ6) and large atretic (nZ5) follicles were analyzed using Exiqon's miRCURY LNA microRNA Array 6th gen, followed by qPCR validation. A total of 17 and 57 sequences were differentially expressed (greater than or equal to twofold; P!0.05) between large healthy and each of small and large atretic follicles respectively. Bovine miRNAs confirmed to be upregulated in large healthy follicles relative to small follicles (bta-miR-144, bta-miR-202, bta-miR-451, bta-miR-652, and bta-miR-873) were further characterized. Three of these miRNAs (bta-miR-144, bta-miR-202, and bta-miR-873) were also downregulated in large atretic follicles relative to large healthy follicles. Within the follicle, these miRNAs were predominantly expressed in mural granulosa cells. Further, body-wide screening revealed that bta-miR-202, but not other miRNAs, was expressed exclusively in the gonads. Finally, a total of 1359 predicted targets of the five miRNAs enriched in large healthy follicles were identified, which mapped to signaling pathways involved in follicular cell proliferation, steroidogenesis, prevention of premature luteinization, and oocyte maturation.

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MiR-21 Induced Angiogenesis through AKT and ERK Activation and HIF-1α Expression

Cited by 433 publications

References 48 publications

MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation

MicroRNA signature of inflamed lymphatic endothelium and role of miR-9 in lymphangiogenesis and inflammation

Lipoxin A4 activates alveolar epithelial sodium channel gamma via the microRNA-21/PTEN/AKT pathway in lipopolysaccharide-induced inflammatory lung injury

Characterization of microRNAs differentially expressed during bovine follicle development

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