JunB regulates angiogenesis and neurovascular parallel alignment in mouse embryonic skin

Yoshitomi, Yasuo; Ikeda, Takayuki; Saito, Hiroyoshi; Yoshitake, Yoshino; Ishigaki, Yasuhito; Hatta, Toshihisa; Kato, Nobuo; Yonekura, Hideto

doi:10.1242/jcs.196303

Cited by 22 publications

(23 citation statements)

References 39 publications

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“…Infil‐trating inflammatory cells such as monocytes, endothelial cells, and local matrix degradation might be sources of VEGF that can increase alveolar capillary permeability. Recently, Yoshitomi et al () reported that VEGF was up regulated in JunB‐over expressing endothelial cells, suggesting that VEGF is induced by JunB. Additionally, AP‐1 an intracellular transcription activator, binds to the promoter region of the VEGF gene (Lee et al, ) and upregulates VEGF expression in different cancers (Bancroft et al, ; Chen, Chen, Pang, Hu, & Zhang, ; Yin et al, ).…”

Section: Discussionmentioning

confidence: 99%

The MAPK‐activator protein‐1 signaling regulates changes in lung tissue of rat exposed to hypobaric hypoxia

Singh

Yadav

Kumar

et al. 2018

Journal Cellular Physiology

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This study reports the role of MAPKs (JNK, ERK, and p38), and activator protein-1 (AP-1) transcription factor in the hypobaric hypoxia induced change in lung tissue. Healthy male Sprague-Dawley rats were exposed to hypobaric hypoxia for 6, 12, 24, 48, 72, and 120 hr. Hypoxia resulted in significant increase in reactive oxygen species (ROS), vascular endothelial growth factor (VEGF) and decreased nitric oxide (NO), these act as signaling molecules for activation of MAPK and also contribute in development of vascular leakage (an indicator of pulmonary edema) as confirmed by histological studies. Our results confirmed JNK activation as an immediate early response (peaked at 6-48 hr), activation of ERKs (peaked at 24-72 hr) and p38 (peaked at 72-120 hr) as a secondary response to hypoxia. The MAPK pathway up regulated its downstream targets phospho c-Jun (peaked at 6-120 hr), JunB (peaked at 24-120 hr) however, decreased c-Fos, and JunD levels. DNA binding activity also confirmed activation of AP-1 transcription factor in lung tissue under hypobaric hypoxia. Further, we analyzed the proliferative and inflammatory genes regulated by different subunits of AP-1 to explore its role in vascular leakage. Increased expression of cyclin D1 (peaked at 12-72 hr) and p16 level (peaked at 48-120 hr) were correlated to the activation of c-jun, c-Fos and JunB. Administration of NFκB inhibitor caffeic acid phenethyl ester (CAPE) and SP600125 (JNK inhibitor) had no effect on increased levels of Interferon-γ (IFN-γ), Interleukin-1 (IL-1), and Tumor Necrosis Factor-α (TNF-α) thereby confirming the involvement of AP-1 as well as NFκB in inflammation. Expression of c-jun, c-Fos were correlated with activation of proliferative genes and JunB, Fra-1 with pro-inflammatory cytokines. In conclusion immediate response to hypobaric hypoxia induced c-Jun:c-Fos subunits of AP-1; responsible for proliferation that might cause inhomogeneous vasoconstriction leading to vascular leakage and inflammation at increased duration of hypobaric hypoxia exposure.

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Section: Discussionmentioning

confidence: 99%

The MAPK‐activator protein‐1 signaling regulates changes in lung tissue of rat exposed to hypobaric hypoxia

Singh

Yadav

Kumar

et al. 2018

Journal Cellular Physiology

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“…Microarray analyses were performed as described previously (Yoshitomi et al, 2017). Briefly, total RNA was extracted using TRIZOL reagent (Invitrogen) and was purified using RNeasy Mini kits (Qiagen, Valencia, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Lentiviral vector production was performed as described previously (Yoshitomi et al, 2017). Briefly, the human Otx2 (RefSeq NM_001286481.1) open reading frame was amplified using RT-PCR using primers listed in and was cloned into pCDH vectors (System Biosciences, Palo Alto, CA).…”

Section: Methodsmentioning

confidence: 99%

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Ultraviolet B-induced Otx2 expression in lens epithelial cells promotes epithelial–mesenchymal transition

et al. 2019

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Ultraviolet (UV) radiation of eyes is a major risk factor for cataractogenesis, although the molecular mechanisms underlying this process remain poorly understood and genes that are affected by UV radiation have not been fully identified. In this study, we examined the UV-related gene regulation in lens epithelial cells (LECs) of mouse eyes and investigated the molecular mechanisms of UV-triggered cataractogenesis. Forty-one genes were significantly upregulated in LECs following UVB exposure in vivo in two independent experiments. Among these, Otx2 was strongly upregulated in LECs, suggesting that it may act as an upstream regulator of UVB-induced changes in gene expression. Accordingly, Otx2 overexpression in LECs in vitro induced morphological changes in cell shapes. Epithelial–mesenchymal transition (EMT)-related molecules, such as TGFβ2, αSMA and fibronectin were upregulated in Otx2-overexpressing LECs, concomitant with suppression of lens fiber cell marker genes, such as CRYAA and DNASEIIB. In vitro experiments suggested that UVB upregulated Otx2 through hydrogen peroxide generation. Aberrant upregulation of Otx2 in LECs following UV irradiation induces the EMT and alteration of the lens cell characteristics, likely contributing to cataractogenesis.

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“…Appropriate directional expansion in both structures depends on common repulsive and attractive cues such as neuropilins, ephrins, and JunB. 8,[11][12][13] Additionally, nerves locally generate vascular endothelial growth factors, crucial angiogenesis and lymphangiogenesis stimulators, and vessels supply artemin and neurotrophin 3, key mediators attracting axons. 8,[14][15][16] Shared growth cues and bidirectional communication could explain why disorganized vascular growth found in facial VANs impacts patterning of FN branches.…”

Section: Introductionmentioning

confidence: 99%

Facial Nerve Branching Patterns Vary With Vascular Anomalies

et al. 2020

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Objectives: At our institution, in vivo facial nerve mapping (FNM) is used during vascular anomaly (VAN) surgeries involving the facial nerve (FN) to create an FN map and prevent injury. During mapping, FN anatomy seemed to vary with VAN type. This study aimed to characterize FN branching patterns compared to published FN anatomy and VAN type. Study Design: Retrospective study of surgically relevant facial nerve anatomy. Methods: VAN patients (n = 67) with FN mapping between 2005 and 2018 were identified. Results included VAN type, FN relationship to VAN, FNM image with branch pattern, and surgical approach. A Fisher exact test compared FN relationships and surgical approach between VAN pathology, and FN branching types to published anatomical studies. MATLAB quantified FN branching with Euclidean distances and angles. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) analyzed quantitative FN patterns amongst VAN types. Results: VANs included were hemangioma, venous malformation, lymphatic malformation, and arteriovenous malformation (n = 17, 13, 25, and 3, respectively). VAN FN patterns differed from described FN anatomy (P < .001). PCA and HCA in MATLAB-quantified FN branching demonstrated no patterns associated with VAN pathology (P = .80 and P = .91, one-way analysis of variance for principle component 1 (PC1) and priniciple component 2 (PC2), respectively). FN branches were usually adherent to hemangioma or venous malformation as compared to coursing through lymphatic malformation (both P = .01, Fisher exact). Conclusions: FN branching patterns identified through electrical stimulation differ from cadaveric dissection determined FN anatomy. This reflects the high sensitivity of neurophysiologic testing in detecting small distal FN branches. Elongated FN branches traveling through lymphatic malformation may be related to abnormal nerve patterning in these malformations.

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JunB regulates angiogenesis and neurovascular parallel alignment in mouse embryonic skin

Cited by 22 publications

References 39 publications

The MAPK‐activator protein‐1 signaling regulates changes in lung tissue of rat exposed to hypobaric hypoxia

The MAPK‐activator protein‐1 signaling regulates changes in lung tissue of rat exposed to hypobaric hypoxia

Ultraviolet B-induced Otx2 expression in lens epithelial cells promotes epithelial–mesenchymal transition

Facial Nerve Branching Patterns Vary With Vascular Anomalies

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