scholarly journals HYBID (alias KIAA1199/CEMIP) and hyaluronan synthase coordinately regulate hyaluronan metabolism in histamine-stimulated skin fibroblasts

2020 ◽  
Vol 295 (8) ◽  
pp. 2483-2494
Author(s):  
Hiroyuki Yoshida ◽  
Mika Aoki ◽  
Aya Komiya ◽  
Yoko Endo ◽  
Keigo Kawabata ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Fold Increase ◽  
Histamine Receptor ◽  
Skin Fibroblasts ◽  
Dependent Manner ◽  
Skin Damage ◽  
Photoaged Skin ◽  
Molecular Sizes ◽  
Ha Synthase ◽  
Hyaluronan Binding

The immune-regulatory compound histamine is involved in the metabolism of the essential skin component hyaluronan (HA). We previously reported that histamine up-regulates the expression of HYBID (hyaluronan-binding protein involved in hyaluronan depolymerization, also called CEMIP or KIAA1199), which plays a key role in HA degradation. However, no information is available about histamine's effects on HA synthase (HAS) expression, the molecular sizes of HA species produced, and histamine receptors and their signaling pathways in skin fibroblasts. Moreover, histamine's effects on photoaged skin remain elusive. Here, we show that histamine increases HA degradation by up-regulating HYBID and down-regulating HAS2 in human skin fibroblasts in a dose- and time-dependent manner and thereby decreases the total amounts and sizes of newly produced HA. Histamine H1 blocker abrogated the histamine effects on HYBID up-regulation, HAS2 suppression, and HA degradation. Histamine H1 agonist exhibited effects on HA levels, composition, and breakdown similar to those of histamine. Of note, blockade of protein kinase Cδ or PI3K–Akt signaling abolished histamine-mediated HYBID stimulation and HAS2 suppression, respectively. Immunohistochemical experiments revealed a significant ∼2-fold increase in tryptase-positive mast cells in photoaged skin, where HYBID and HAS2 expression levels were increased and decreased, respectively, compared with photoprotected skin. These results indicate that histamine controls HA metabolism by up-regulating HYBID and down-regulating HAS2 via distinct signaling pathways downstream of histamine receptor H1. They further suggest that histamine may contribute to photoaged skin damage by skewing HA metabolism toward degradation.

scholarly journals Protective Effect of Sulfated Polysaccharides from Celluclast-Assisted Extract of Hizikia fusiforme Against Ultraviolet B-Induced Skin Damage by Regulating NF-κB, AP-1, and MAPKs Signaling Pathways In Vitro in Human Dermal Fibroblasts

Marine Drugs ◽  
2018 ◽  
Vol 16 (7) ◽  
pp. 239 ◽  
Author(s):  
Lei Wang ◽  
WonWoo Lee ◽  
Jae Oh ◽  
Yong Cui ◽  
BoMi Ryu ◽  
...  
Keyword(s):  
Protective Effect ◽  
Signaling Pathways ◽  
Dermal Fibroblasts ◽  
Sulfated Polysaccharides ◽  
Dependent Manner ◽  
Human Dermal Fibroblasts ◽  
Skin Damage ◽  
Hizikia Fusiforme ◽  
Hdf Cells

Our previous study evaluated the antioxidant activities of sulfated polysaccharides from Celluclast-assisted extract of Hizikia fusiforme (HFPS) in vitro in Vero cells and in vivo in zebrafish. The results showed that HFPS possesses strong antioxidant activity and suggested the potential photo-protective activities of HFPS. Hence, in the present study, we investigated the protective effects of HFPS against ultraviolet (UV) B-induced skin damage in vitro in human dermal fibroblasts (HDF cells). The results indicate that HFPS significantly reduced intracellular reactive oxygen species (ROS) level and improved the viability of UVB-irradiated HDF cells in a dose-dependent manner. Furthermore, HFPS significantly inhibited intracellular collagenase and elastase activities, remarkably protected collagen synthesis, and reduced matrix metalloproteinases (MMPs) expression by regulating nuclear factor kappa B (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinases (MAPKs) signaling pathways in UVB-irradiated HDF cells. These results suggest that HFPS possesses strong UV protective effect, and can be a potential ingredient in the pharmaceutical and cosmetic industries.

scholarly journals Role of HYBID (Hyaluronan Binding Protein Involved in Hyaluronan Depolymerization), Alias KIAA1199/CEMIP, in Hyaluronan Degradation in Normal and Photoaged Skin

2019 ◽  
Vol 20 (22) ◽  
pp. 5804 ◽  
Author(s):  
Hiroyuki Yoshida ◽  
Yasunori Okada
Keyword(s):  
Binding Protein ◽  
Normal Skin ◽  
Collagen Fibers ◽  
Skin Fibroblasts ◽  
Photoaged Skin ◽  
Skin Photoaging ◽  
Skin Wrinkling ◽  
Initial Process ◽  
Hyaluronan Binding

Photoaged skin is characterized clinically by apparent manifestations such as wrinkles and sagging, and histologically by an accumulation of abnormal elastin and a severe loss of collagen fibers in the dermis. Quantitative and qualitative alterations in elastin and collagens are considered to be responsible for the formation of wrinkles and sagging. However, since the integrity of elastin and collagen fibers in the dermis is maintained by their interactions with hyaluronan (HA) and a proteoglycan network structure, HA degradation may be the initial process, prior to the breakdown of the fibrillary components, leading to wrinkles and sagging in photoaged skin. We have recently discovered a new HA-degrading mechanism mediated by HYBID (hyaluronan binding protein involved in hyaluronan depolymerization), alias KIAA1199/CEMIP, in human skin fibroblasts, and examined the implication of HYBID for skin photoaging. In this review, we give an overview of the characteristics of HYBID and its prospective roles in HA turnover in normal skin and excessive HA degradation in photoaged skin. In addition, we describe our data on the inhibition of HYBID activity and expression by plant extracts in skin fibroblasts; and propose novel strategies to prevent or improve photoaging symptoms, such as skin wrinkling, by inhibition of HYBID-mediated HA degradation.

Preventive Effects of β-Thujaplicin Against UVB-Induced MMP-1 and MMP-3 mRNA Expressions in Skin Fibroblasts

2012 ◽  
Vol 40 (02) ◽  
pp. 387-398 ◽  
Author(s):  
Jong Yuh Cherng ◽  
Li Yin Chen ◽  
Mei Fen Shih
Keyword(s):  
Gene Expression ◽  
Vitamin E ◽  
Vitamin C ◽  
Human Skin ◽  
Antimicrobial Activities ◽  
Skin Fibroblasts ◽  
Premature Aging ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Dependent Manner ◽  
Skin Damage

Solar UV radiation damages human skin by affecting skin tone and resiliency and leads to premature aging (photoaging). The skin damage is caused by the activation of the AP-1 transcription factor, which increases matrix metalloproteinase (MMP) expression and collagen degradation. An increase of interleukin (IL)-6 is also correlated with the activation of MMP-1 expression. β-thujaplicin has shown both acaricidal and antimicrobial activities. Also, β-thujaplicin has been shown to be protective against apoptosis due to the oxidative effects of UV irradiation. However, the effect of β-thujaplicin on UVB-induced MMPs had not been investigated. In this study, after UVB exposure, MMP-1 and IL-6 production in human skin fibroblasts was examined in the presence of β-thujaplicin, vitamin C, and vitamin E. The expression of MMP-1, MMP-3, tissue inhibitor of metalloproteinase (TIMP-1, TIMP-3) and procollagen mRNA was also investigated. Results showed that UVB-induced MMP-1 production was suppressed by the β-thujaplicin treatment in a dose-dependent manner, but not by vitamin C and vitamin E. β-thujaplicin also prevented the up-regulation of MMP-1 and MMP-3 mRNA. Moreover, the UVB-suppressed procollagen gene expression was restored to normal by β-thujaplicin. Neither UVB nor β-thujaplicin affected the mRNA expression of TIMP-1 and TIMP-3. The IL-6 production induced by UVB was lower in β-thujaplicin treated fibroblasts than in the controls. In conclusion, this study shows the capability of β-thujaplicin in preventing MMP-1 production due to UVB irradiation via inhibition of MMP gene expression. Importantly, the UVB-suppressed procollagen gene expression can be restored to normal by β-thujaplicin. These findings indicate that β-thujaplicin is a promising and potent agent to inhibit UVB-induced MMP-1 and MMP-3 gene expression in skin fibroblasts.

Insight into Mechanistic Action of Thymoquinone Induced Melanogenesis in Cultured Melanocytes

2019 ◽  
Vol 26 (12) ◽  
pp. 910-918
Author(s):  
Kamal U. Zaidi ◽  
Firoz N. Khan ◽  
Sharique A. Ali ◽  
Kausar P. Khan
Keyword(s):  
Western Blot ◽  
Signaling Pathways ◽  
Cell Line ◽  
Melanoma Cell ◽  
Melanoma Cell Line ◽  
Protein Kinase Inhibitors ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
B16f10 Melanoma ◽  
B16f10 Melanoma Cell

Background: Melanin plays a crucial role in camouflage, social communication and protection against harmful ultraviolet radiations. Melanin is synthesized by melanocytes through melanogenesis and several intrinsic and extrinsic factors are involved during the process. Any change occuring in the normal melanogenesis process can cause severe pigmentation problems of hypopigmentation or hyperpigmentation. Objective: The present study is based on the evaluation of the effect of thymoquinone on melanogenesis and their possible mechanism of action using the B16F10 melanoma cell line for the production via blocking signaling pathways. Methods: Phase contrast microscopy, cell viability, tyrosinase activity, melanin content and western blot analysis were used in the present study. Results: In the present investigation, cultured melanocytes exhibit that the stimulation of melanin synthesis when treated with thymoquinone. Tyrosinase activity and melanin production in B16F10 melanoma cell line was increased in doze-dependent manner. In western blot, we investigated the involvement of the cAMP/PKA pathway in thymoquinone induced melanogenesis. It was observed protein kinase inhibitors PKA, PKC, PKB and MEK1 decreased the stimulatory effects of thymoquinone from 11.45- fold value to 8.312, 6.631, 4.51, and 7.211-fold value, respectively. However, the results also prove that thymoquinone may partially induce tyrosinase expression via PKA, PKB, PKC and MEK1 signaling pathways. Conclusion: The present finding proposed that thymoquinone is a protective challenger for melanogenesis and it might be useful for the treatment of hypopigmentary disorders.

scholarly journals Proteomic Changes during the Dermal Toxicity Induced by Nemopilema nomurai Jellyfish Venom in HaCaT Human Keratinocyte

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 311
Author(s):  
Indu Choudhary ◽  
Duhyeon Hwang ◽  
Jinho Chae ◽  
Wonduk Yoon ◽  
Changkeun Kang ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Skin Damage ◽  
Nemopilema Nomurai ◽  
Concentration Dependent Manner ◽  
Local Skin ◽  
Maldi Tof Ms ◽  
Maldi Tof ◽  
Proteome Level ◽  
Tof Ms ◽  
Jellyfish Venom

Jellyfish venom is well known for its local skin toxicities and various lethal accidents. The main symptoms of local jellyfish envenomation include skin lesions, burning, prickling, stinging pain, red, brown, or purplish tracks on the skin, itching, and swelling, leading to dermonecrosis and scar formation. However, the molecular mechanism behind the action of jellyfish venom on human skin cells is rarely understood. In the present study, we have treated the human HaCaT keratinocyte with Nemopilema nomurai jellyfish venom (NnV) to study detailed mechanisms of actions behind the skin symptoms after jellyfish envenomation. Using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF/MS), cellular changes at proteome level were examined. The treatment of NnV resulted in the decrease of HaCaT cell viability in a concentration-dependent manner. Using NnV (at IC50), the proteome level alterations were determined at 12 h and 24 h after the venom treatment. Briefly, 70 protein spots with significant quantitative changes were picked from the gels for MALDI-TOF/MS. In total, 44 differentially abundant proteins were successfully identified, among which 19 proteins were increased, whereas 25 proteins were decreased in the abundance levels comparing with their respective control spots. DAPs involved in cell survival and development (e.g., Plasminogen, Vinculin, EMILIN-1, Basonuclin2, Focal adhesion kinase 1, FAM83B, Peroxisome proliferator-activated receptor-gamma co-activator 1-alpha) decreased their expression, whereas stress or immune response-related proteins (e.g., Toll-like receptor 4, Aminopeptidase N, MKL/Myocardin-like protein 1, hypoxia up-regulated protein 1, Heat shock protein 105 kDa, Ephrin type-A receptor 1, with some protease (or peptidase) enzymes) were up-regulated. In conclusion, the present findings may exhibit some possible key players during skin damage and suggest therapeutic strategies for preventing jellyfish envenomation.

scholarly journals Elucidation of Melanogenesis-Associated Signaling Pathways Regulated by Argan Press Cake in B16 Melanoma Cells

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2697
Author(s):  
Thouria Bourhim ◽  
Myra O. Villareal ◽  
Chemseddoha Gadhi ◽  
Hiroko Isoda
Keyword(s):  
Signaling Pathways ◽  
Press Cake ◽  
Global Gene Expression ◽  
Melanoma Cells ◽  
B16 Melanoma ◽  
Dependent Manner ◽  
Melanin Biosynthesis ◽  
B16 Melanoma Cells ◽  
Pigmentary Disorders ◽  
Argan Oil

The beneficial effect on health of argan oil is recognized worldwide. We have previously reported that the cake that remains after argan oil extraction (argan press-cake or APC) inhibits melanogenesis in B16 melanoma cells in a time-dependent manner without cytotoxicity. In this study, the global gene expression profile of B16 melanoma cells treated with APC extract was determined in order to gain an understanding of the possible mechanisms of action of APC. The results suggest that APC extract inhibits melanin biosynthesis by down-regulating microphthalmia-associated transcription factor (Mitf) and its downstream signaling pathway through JNK signaling activation, and the inhibition of Wnt/β-catenin and cAMP/PKA signaling pathways. APC extract also prevented the transport of melanosomes by down-regulating Rab27a expression. These results suggest that APC may be an important natural skin whitening product and pharmacological agent used for clinical treatment of pigmentary disorders.

Tamoxifen inhibits phorbol ester stimulated osteoclastic bone resorption: An effect mediated by calmodulin

2000 ◽  
Vol 78 (6) ◽  
pp. 715-723 ◽  
Author(s):  
John P Williams ◽  
Margaret A McKenna ◽  
Allyn M Thames III ◽  
Jay M McDonald
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Bone Resorption ◽  
Phorbol Ester ◽  
Phorbol Esters ◽  
Fold Increase ◽  
Dependent Manner ◽  
Osteoclast Activity ◽  
Kinase C ◽  
Protein Kinase Cα

Tamoxifen inhibits bone resorption by disrupting calmodulin-dependent processes. Since tamoxifen inhibits protein kinase C in other cells, we compared the effects of tamoxifen and the phorbol ester, phorbol myristate acetate, on osteoclast activity. Phorbol esters stimulate bone resorption and calmodulin levels four-fold (k0.5 = 0.1–0.3 µM). In contrast, tamoxifen inhibited osteoclast activity ~60% with an IC50 of 1.5 µM, had no apparent effect on protein kinase C activity in whole-cell lysates, and reduced protein kinase Cα recovered by immunoprecipitation 75%. Phorbol esters stimulated resorption in a time-dependent manner that was closely correlated with a similar-fold increase in calmodulin. Protein kinase Cα, β, δ, ε, and ζ were all down-regulated in response to phorbol ester treatment. Tamoxifen and trifluoperazine inhibited PMA-dependent increases in bone resorption and calmodulin by 85 ± 10%. Down-regulation of protein kinase C isoforms by phorbol esters suggests that the observed increases in bone resorption and calmodulin levels are most likely due to a mechanism independent of protein kinase C and dependent on calmodulin. In conclusion, the data suggest that protein kinase C negatively regulates calmodulin expression and support the hypothesis that the effects of both phorbol esters and tamoxifen on osteoclast activity is mediated by calmodulin.Key words: osteoclast, calmodulin, tamoxifen, osteoporosis, protein kinase C.

Candida tropicalis induces pro-inflammatory cytokine production, NF-κB and MAPKs pathways regulation, and dectin-1 activation

2018 ◽  
Vol 64 (12) ◽  
pp. 937-944 ◽  
Author(s):  
Zhimin Duan ◽  
Qing Chen ◽  
Rong Zeng ◽  
Leilei Du ◽  
Caixia Liu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Cytokine ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Downstream Signaling ◽  
Tnf Α ◽  
Mitogen Activated Protein

The prevalence of Candida infection induced by non-albicans Candida (NAC) species is increasing. However, as a common NAC species, C. tropicalis has received much less study in terms of host immunity than C. albicans has. In this study, we evaluated the pro-inflammatory cytokine responses evoked by C. tropicalis and determined whether dectin-1 and downstream NF-κB and mitogen-activated protein kinases (MAPKs) signaling pathways played roles in inflammation in human peripheral blood mononuclear cells (PBMCs) and THP-1 macrophage-like cells. Exposure of PBMCs and THP-1 macrophage-like cells to C. tropicalis led to the enhanced gene expression and secretion of TNF-α and IL-6 in a time- and dose-dependent manner. THP-1 macrophage-like cells being challenged by C. tropicalis resulted in the activation of the NF-κB, p38, and ERK1/2 MAPK signaling pathways. We also found that the expression of dectin-1 was increased with C. tropicalis treatment. These data reveal that dectin-1 may play a role in sensing the inflammation response induced by C. tropicalis and that NF-κB and MAPK are involved in the downstream signaling pathways in macrophages.

scholarly journals The Crossroads between RAS and RHO Signaling Pathways in Cellular Transformation, Motility and Contraction

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 819
Author(s):  
Olga Soriano ◽  
Marta Alcón-Pérez ◽  
Miguel Vicente-Manzanares ◽  
Esther Castellano
Keyword(s):  
Signaling Pathways ◽  
Actin Polymerization ◽  
Mapk Pathway ◽  
Human Cancer ◽  
Cellular Transformation ◽  
Dependent Manner ◽  
Rho Proteins ◽  
Filament Assembly ◽  
Multiple Signaling ◽  
Mechanical Feedback

Ras and Rho proteins are GTP-regulated molecular switches that control multiple signaling pathways in eukaryotic cells. Ras was among the first identified oncogenes, and it appears mutated in many forms of human cancer. It mainly promotes proliferation and survival through the MAPK pathway and the PI3K/AKT pathways, respectively. However, the myriad proteins close to the plasma membrane that activate or inhibit Ras make it a major regulator of many apparently unrelated pathways. On the other hand, Rho is weakly oncogenic by itself, but it critically regulates microfilament dynamics; that is, actin polymerization, disassembly and contraction. Polymerization is driven mainly by the Arp2/3 complex and formins, whereas contraction depends on myosin mini-filament assembly and activity. These two pathways intersect at numerous points: from Ras-dependent triggering of Rho activators, some of which act through PI3K, to mechanical feedback driven by actomyosin action. Here, we describe the main points of connection between the Ras and Rho pathways as they coordinately drive oncogenic transformation. We emphasize the biochemical crosstalk that drives actomyosin contraction driven by Ras in a Rho-dependent manner. We also describe possible routes of mechanical feedback through which myosin II activation may control Ras/Rho activation.

Phosphatidylinositol 3-kinase mediates integrin-dependent NF-(κ)B and MAPK activation through separate signaling pathways

2001 ◽  
Vol 114 (8) ◽  
pp. 1579-1589 ◽  
Author(s):  
M. Reyes-Reyes ◽  
N. Mora ◽  
A. Zentella ◽  
C. Rosales
Keyword(s):  
Signaling Pathways ◽  
Mapk Pathway ◽  
Mek Inhibitor ◽  
Small Gtpase ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Dependent Manner ◽  
Monocytic Leukemia ◽  
Monocytic Cells ◽  
Mapk Activation

Integrin-mediated signals play an important but poorly understood role in regulating many leukocyte functions. In monocytes and monocytic leukemia cells, (β)1 integrin-mediated adhesion results in a strong induction of immediate-early genes that are important in inflammation. To investigate the signaling pathways from integrins in monocytic cells, THP-1 cells were stimulated via (β)1 integrins by binding to fibronectin and by crosslinking the integrins with specific monoclonal antibodies. The involvement of MAPK and PI 3-K on nuclear factor (κ)B (NF-(κ)B) activation was then analyzed. We found that integrins activated both NF-(κ)B and MAPK in a PI 3-K-dependent manner, as wortmannin and LY294002 blocked these responses. However, the specific MEK inhibitor PD98059 did not prevent integrin-mediated NF-(κ)B activation. In contrast, a dominant negative mutant of Rac completely prevented NF-(κ)B activation, but it did not affect MAPK activation. These results indicate that integrin signaling to NF-(κ)B is not mediated by the MAPK pathway, but rather by the small GTPase Rac. In addition, a dominant negative form of Ρ augmented NF-(κ)B activation and blocked MAPK activation, implying that these two pathways are in competition with each other. These data suggest that integrins activate different signaling pathways in monocytic cells. One uses PI 3-K and Rac to activate NF-(κ)B, while the other uses PI 3-K, MEK, and MAPK to activate other nuclear factors, such as Elk-1.

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