Role of Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) in Keratinocyte Differentiation

Park, Kwang‐Hyun; Kim, Kwang N.; Park, Dae-Ryoung; Jang, Kyu Yoon; Kim, Uh-Hyun

doi:10.1038/jid.2015.43

Cited by 8 publications

(11 citation statements)

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“…These data suggest that TIP39 increases [Ca 2+ ]i via PTH2R, and regulates calcium homeostasis in low extracellular calcium conditions. Furthermore, pretreatment with inhibitors of the IP3 pathway, such as calmodulin, phospholipase C, and inositol 1,4,5-trisphosphate receptors, reduced the effects of TIP39 from 17.8% to 5.7%, 6.0%, and 7.1%, respectively (Figure 4e, lower graphs), but the inhibitor of nicotinic acid adenine dinucleotide phosphate that targets acidic endolysosomal Ca 2+ stores (Park et al, 2015) and sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase did not effectively block the TIP39 response (12.2% and 13.6%, respectively) (Figure 4e, upper-right two graphs).…”

Section: Resultsmentioning

confidence: 99%

The Parathyroid Hormone Second Receptor PTH2R and its Ligand Tuberoinfundibular Peptide of 39 Residues TIP39 Regulate Intracellular Calcium and Influence Keratinocyte Differentiation

Sato

Muto

Zhang

et al. 2016

Journal of Investigative Dermatology

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Genes related to the parathyroid hormone (PTH) influence cutaneous immune defense and development, but the full functions of the PTH family in cutaneous biology remain incompletely understood. In this study, we examined the expression and potential functions of the PTH second receptor (PTH2R) and its ligand, the tuberoinfundibular peptide of 39 residues (TIP39), in the skin. TIP39 and PTH2R mRNA and protein were detectable in both human and mouse skin, and in cultured keratinocytes and adipocytes. TIP39 was observed in the basal layer of human skin, whereas PTH2R was detected in the spinous to granular layer. The subcellular localization of TIP39 in keratinocytes changed during calcium-induced differentiation and shifted to colocalize with PTH2R at the membrane. The addition of recombinant TIP39 to normal human keratinocytes in culture induced an increase in intercellular calcium and triggered aspects of terminal differentiation including decreased keratin-14 and increased involucrin expression. Consistent with these observations, PTH2R−/− mice were observed to have increased epidermal thickness. In summary, identification of TIP39 and its receptor in the epidermis reveals an additional PTH family member that is expressed in the skin and may influence keratinocyte function.

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Section: Resultsmentioning

confidence: 99%

The Parathyroid Hormone Second Receptor PTH2R and its Ligand Tuberoinfundibular Peptide of 39 Residues TIP39 Regulate Intracellular Calcium and Influence Keratinocyte Differentiation

Sato

Muto

Zhang

et al. 2016

Journal of Investigative Dermatology

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“…Recent studies have reported that appropriate drugs, activator protein-1, or exogenous mechanical forces on keratinocytes can accelerate wound healing [34][35][36]. Niyonsaba also reported that hBD-2 increases the concentration of intracellular Ca 2+ [8].…”

Section: Discussionmentioning

confidence: 99%

The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

Mi¹,

Liu²,

Liu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Antimicrobial peptides are effective promoters of wound healing but are susceptible to degradation. In this study, we replaced the GIGDP unit on the N-terminal of the endogenous human antimicrobial peptide hBD-2 with APKAM to produce A-hBD-2 and analyzed the effect on wound healing both in vitro and in vivo. Methods: The effects of A-hBD-2 and hBD-2 on cytotoxicity and proliferation in keratinocytes were assessed by Cell Counting Kit-8 assay. The structural stability and antimicrobial activity of hBD-2 and A-hBD-2 were evaluated against Staphylococcus aureus. RNA and proteins levels were evaluated by real-time PCR and western blotting, respectively. Cell migration was evaluated using a transwell assay. Cell cycle analysis was performed by flow cytometry. Wound healing was assessed in Sprague-Dawley rats. Epidermal thickness was evaluated by hematoxylin and eosin staining. Results: We found that hBD-2 exhibited cytotoxicity at high concentrations and decreased the structural stability in the presence of high sodium chloride concentrations. A-hBD-2 exhibited increased structural stability and antimicrobial activity, and had lower cytotoxicity in keratinocytes. A-hBD-2 increased the migration and proliferation of keratinocytes via phosphorylation of EGFR and STAT3 and suppressed terminal differentiation of keratinocytes. We also found that A-hBD-2 elicited mobilization of intracellular Ca²⁺ and stimulated keratinocytes to produce pro- and anti-inflammatory cytokines and chemokines via phospholipase C activation. Furthermore, A-hBD-2 promoted wound healing in vivo. Conclusion: Our data suggest that A-hBD-2 may be a promising candidate therapy for wound healing.

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“…After centrifugation at 15,000× g for 10 min, the aqueous layer was collected and neutralized with 20 mM sodium phosphate (pH 8.0). The enzyme product, cADPR, was measured by modification of the cycling method described previously [68]. To remove all contaminating nucleotides, the samples were incubated overnight with the following hydrolytic enzymes at 37 °C: 0.44 units/ml nucleotide pyrophosphatase, 12.5 units/ml alkaline phosphatase, 0.0625 units/ml NAD glycohydrolase, and 2.5 mM MgCl 2 in 20 mM sodium phosphate buffer (pH 8.0).…”

Section: Methodsmentioning

confidence: 99%

An immunohistochemical, enzymatic, and behavioral study of CD157/BST-1 as a neuroregulator

et al. 2017

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BackgroundRecent rodent and human studies provide evidence in support of the fact that CD157, well known as bone marrow stromal cell antigen-1 (BST-1) and a risk factor in Parkinson’s disease, also meaningfully acts in the brain as a neuroregulator and affects social behaviors. It has been shown that social behaviors are impaired in CD157 knockout mice without severe motor dysfunction and that CD157/BST1 gene single nucleotide polymorphisms are associated with autism spectrum disorder in humans. However, it is still necessary to determine how this molecule contributes to the brain’s physiological and pathophysiological functions.MethodsTo gain fresh insights about the relationship between the presence of CD157 in the brain and its enzymatic activity, and aberrant social behavior, CD157 knockout mice of various ages were tested.ResultsCD157 immunoreactivity colocalized with nestin-positive cells and elements in the ventricular zones in E17 embryos. Brain CD157 mRNA levels were high in neonates but low in adults. Weak but distinct immunoreactivity was detected in several areas in the adult brain, including the amygdala. CD157 has little or no base exchange activity, but some ADP-ribosyl cyclase activity, indicating that CD157 formed cyclic ADP-ribose but much less nicotinic acid adenine dinucleotide phosphate, with both mobilizing Ca2+ from intracellular Ca2+ pools. Social avoidance in CD157 knockout mice was rescued by a single intraperitoneal injection of oxytocin.ConclusionsCD157 may play a role in the embryonic and adult nervous systems. The functional features of CD157 can be explained in part through the production of cyclic ADP-ribose rather than nicotinic acid adenine dinucleotide phosphate. Further experiments are required to elucidate how the embryonic expression of CD157 in neural stem cells contributes to behaviors in adults or to psychiatric symptoms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-017-0350-7) contains supplementary material, which is available to authorized users.

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Role of Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) in Keratinocyte Differentiation

Cited by 8 publications

References 9 publications

The Parathyroid Hormone Second Receptor PTH2R and its Ligand Tuberoinfundibular Peptide of 39 Residues TIP39 Regulate Intracellular Calcium and Influence Keratinocyte Differentiation

The Parathyroid Hormone Second Receptor PTH2R and its Ligand Tuberoinfundibular Peptide of 39 Residues TIP39 Regulate Intracellular Calcium and Influence Keratinocyte Differentiation

The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

An immunohistochemical, enzymatic, and behavioral study of CD157/BST-1 as a neuroregulator

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