Prostaglandin E2 is critical for the development of niacin-deficiency-induced photosensitivity via ROS production

Sugita, Kazunari; Ikenouchi-Sugita, Atsuko; Nakayama, Yasuko; Yoshioka, Haruna; Nomura, Takashi; Sakabe, Jun‐ichi; Nakahigashi, Kyoko; Kuroda, Etsushi; Uematsu, Satoshi; Nakamura, Jun; Akira, Shizuo; Nakamura, Motonobu; Narumiya, Shuh; Miyachi, Yoshiki; Tokura, Y.; Kabashima, Kenji

doi:10.1038/srep02973

Cited by 20 publications

(22 citation statements)

References 37 publications

(45 reference statements)

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“…5e), are also involved in ROS-mediated apoptosis 25 . RNA-Seq data also showed that negative regulators of ROS ( aplnrb , hsp70.3 , sephs1 and dkc1 ) 26–29 were downregulated in unfit cells, whereas positive regulators ( fabp3 , ptgdsb.1 and krt8 ) 30–32 were upregulated (Fig. 5a and Supplementary Fig.…”

Section: Resultsmentioning

confidence: 81%

Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning in the zebrafish embryo

et al. 2019

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Morphogen signalling forms an activity gradient and instructs cell identities in a signalling strength-dependent manner to pattern developing tissues. However, developing tissues also undergo dynamic morphogenesis, which may produce cells with unfit morphogen signalling and consequent noisy morphogen gradients. Here we show that a cell competition-related system corrects such noisy morphogen gradients. Zebrafish imaging analyses of the Wnt/β-catenin signalling gradient, which acts as a morphogen to establish embryonic anterior-posterior patterning, identify that unfit cells with abnormal Wnt/β-catenin activity spontaneously appear and produce noise in the gradient. Communication between unfit and neighbouring fit cells via cadherin proteins stimulates apoptosis of the unfit cells by activating Smad signalling and reactive oxygen species production. This unfit cell elimination is required for proper Wnt/β-catenin gradient formation and consequent anterior-posterior patterning. Because this gradient controls patterning not only in the embryo but also in adult tissues, this system may support tissue robustness and disease prevention.

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Section: Resultsmentioning

confidence: 81%

Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning in the zebrafish embryo

et al. 2019

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“…Lung alveolar formation starts at P4, and it peaks between P10 and P14 ( 42 , 43 ). Thus, DHEA (10 and 20 mg/kg) ( 44 ) or 6-AN (5 and 10 mg/kg) ( 45 ) was administered daily through i.p. injection to mice for 5 days (between P9 and P13) after they were exposed to hyperoxia for 3 days as neonates.…”

Section: Methodsmentioning

confidence: 99%

The pentose phosphate pathway mediates hyperoxia-induced lung vascular dysgenesis and alveolar simplification in neonates

Gong¹,

Feng²,

Peterson³

et al. 2021

JCI Insight

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Dysmorphic pulmonary vascular growth and abnormal endothelial cell (EC) proliferation are paradoxically observed in premature infants with bronchopulmonary dysplasia (BPD) despite vascular pruning. The pentose phosphate pathway (PPP), a metabolic pathway parallel to glycolysis, generates NADPH as a reducing equivalent and ribose 5-phosphate for nucleotide synthesis. It is unknown whether hyperoxia, a known mediator of BPD in rodent models, alters glycolysis and the PPP in lung ECs. We hypothesized that hyperoxia increases glycolysis and the PPP, resulting in abnormal EC proliferation and dysmorphic angiogenesis in neonatal mice. To test this hypothesis, lung ECs and newborn mice were exposed to hyperoxia and allowed to recover in air. Hyperoxia increased glycolysis and the PPP. Increased PPP, but not glycolysis, caused hyperoxia-induced abnormal EC proliferation. Blocking the PPP reduced hyperoxia-induced glucose-derived deoxynucleotide synthesis in cultured ECs. In neonatal mice, hyperoxia-induced abnormal EC proliferation, dysmorphic angiogenesis, and alveolar simplification were augmented by nanoparticle-mediated endothelial overexpression of phosphogluconate dehydrogenase, the second enzyme in the PPP. These effects were attenuated by inhibitors of the PPP. Altogether, neonatal hyperoxia augments the PPP, causing abnormal lung EC proliferation, dysmorphic vascular development, and alveolar simplification. These novel observations provide mechanisms and potential metabolic targets to prevent BPD-associated vascular dysgenesis.

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“…Niacin deficiency induces reactive oxygen species in KCs, followed by the production of prostaglandin E2 (PGE2). This PGE2 mediates photosensitivity in patients with pellagra [ 115 ]. A study investigating serum Zn levels in 81 pellagra patients showed a significant reduction of serum Zn level in patients with pellagra (69.7 ± 16.8 μg/dL) compared with that in healthy subjects (82.3 ± 34.0 μg/dL) [ 116 ].…”

Section: Human Skin Disorders Associated With Zn Deficiencymentioning

confidence: 99%

Zinc and Skin Disorders

et al. 2018

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The skin is the third most zinc (Zn)-abundant tissue in the body. The skin consists of the epidermis, dermis, and subcutaneous tissue, and each fraction is composed of various types of cells. Firstly, we review the physiological functions of Zn and Zn transporters in these cells. Several human disorders accompanied with skin manifestations are caused by mutations or dysregulation in Zn transporters; acrodermatitis enteropathica (Zrt-, Irt-like protein (ZIP)4 in the intestinal epithelium and possibly epidermal basal keratinocytes), the spondylocheiro dysplastic form of Ehlers-Danlos syndrome (ZIP13 in the dermal fibroblasts), transient neonatal Zn deficiency (Zn transporter (ZnT)2 in the secretory vesicles of mammary glands), and epidermodysplasia verruciformis (ZnT1 in the epidermal keratinocytes). Additionally, acquired Zn deficiency is deeply involved in the development of some diseases related to nutritional deficiencies (acquired acrodermatitis enteropathica, necrolytic migratory erythema, pellagra, and biotin deficiency), alopecia, and delayed wound healing. Therefore, it is important to associate the existence of mutations or dysregulation in Zn transporters and Zn deficiency with skin manifestations.

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Prostaglandin E2 is critical for the development of niacin-deficiency-induced photosensitivity via ROS production

Cited by 20 publications

References 37 publications

Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning in the zebrafish embryo

Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning in the zebrafish embryo

The pentose phosphate pathway mediates hyperoxia-induced lung vascular dysgenesis and alveolar simplification in neonates

Zinc and Skin Disorders

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