scholarly journals c-Myc Upregulated by High Glucose Inhibits HaCaT Differentiation by S100A6 Transcriptional Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Zhang ◽  
Peilang Yang ◽  
Dan Liu ◽  
Min Gao ◽  
Jizhuang Wang ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
High Glucose ◽  
Skin Barrier ◽  
Diabetic Rats ◽  
Keratinocyte Differentiation ◽  
Control Group ◽  
Hacat Cells ◽  
Wound Margin ◽  
Transglutaminase 1 ◽  
Diabetic Wounds

Keratinocyte differentiation dysfunction in diabetic skin is closely related to impaired skin barrier functions. We investigated the effects of c-Myc and S100A6 on Human immortal keratinocyte line (HaCaT) or keratinocyte differentiation and potential mechanisms. The expression levels of differentiation makers such as transglutaminase 1 (TGM1), loricrin (LOR), and keratin 1 (K1) were significantly reduced, while the expression of c-Myc was significantly increased in HaCaT cells cultured in high glucose and wound margin keratinocytes from diabetic rats and human patients. Overexpression of c-Myc caused differentiation dysfunction of HaCaT, while knocking down c-Myc promoted differentiation. High glucose increased the expression of c-Myc and inhibited differentiation in HaCaT cells by activating the WNT/β-catenin pathway. Moreover, inhibition of c-Myc transcriptional activity alleviated the differentiation dysfunction caused by high glucose or overexpression of c-Myc. c-Myc binds to the S100A6 promoter to directly regulate S100A6 expression and high glucose promoted S100A6 transcription. The expression of S100A6 was increased in HaCaT cultured with high glucose and wound margin keratinocytes from diabetic rats and human patients. However, the expression of S100A6 was decreased during normal HaCaT differentiation. HaCaT cells treated with S100A6 recombinant protein showed differentiation dysfunction. The expressions of TGM1, LOR and K1 in knockdown S100A6 HaCaT cells were higher than those in the control group. Overexpression of c-Myc or high glucose caused differentiation dysfunction of HaCaT cells, and was rescued by knocking down S100A6. These findings illustrate a new mechanism by which c-Myc upregulated by high glucose inhibits HaCaT differentiation by directly activating S100A6 transcription. Thus, c-Myc and S100A6 may be potential targets for the treatment of chronic diabetic wounds.

scholarly journals Eucalyptus citriodora extract regulates cutaneous homeostasis including immune dysregulation and skin barrier dysfunction via the modulation of peroxisome proliferator-activated receptor-delta (PPAR-delata) pathway

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Akihiro Aioi ◽  
Takuhiro Yamada
Keyword(s):  
Mrna Expression ◽  
Skin Barrier ◽  
Immune Dysregulation ◽  
Keratinocyte Differentiation ◽  
Hacat Cells ◽  
Skin Disorders ◽  
Eucalyptus Citriodora ◽  
Barrier Dysfunction ◽  
Differentiation Markers ◽  
Transfected Cells

Perturbation of cutaneous homeostasis including immune dysregulation and skin barrier dysfunction evokes skin disorders. In this study, we examined the effect of Eucalyptus citriodora (Euc-c) extract on cytokine production, cell proliferation and cell differentiation in HaCaT cells to elucidate its influence on cutaneous homeostasis. Euc-c suppressed significantly LPS-induced IL-6 and TNF-a-induced IL-8 production from HaCaT cells. Conversely IL-1ra production was significantly enhanced by Euc-c. The expressions of IVL, CERS3 and CERS4, keratinocyte differentiation markers, were upregulated to 3.1, 2.8 and 2.7-fold respectively by Euc-c treatment, compared to the control, while the proliferation was downregulated. The lipid contents in Euc-c-treated cells tended to increase, compared with non-treated cells. To explore the underlying mechanism of these effect, we next performed siRNA experiments against PPAR-b/d. Euc-c enhanced PPAR-b/d mRNA expression to 3.25-fold, while PPAR-b/d mRNA expression in transfected cells was suppressed. The expressions of IVL, CERS3 and CERS4 in transfected cells were suppressed to 1.48, 0.82 and 0.72-fold respectively, concomitant with suppression of PPAR-b/d mRNA expression. These results indicated that Euc-c exerts anti-inflammatory effects and regulates keratinocyte differentiation via the modulation of PPAR-b/d pathway. Therefore, the application of Euc-c is expected to exert beneficial effect on skin disorders evoked by perturbation of skin homeostasis.Key words: Eucalyptus citriodora, PPAR-b/d, inflammation, barrier function, cutaneous homeostasis

scholarly journals Physiological Effects of Manganese Gluconate and Calcium Combination from Saint-Gervais Mont Blanc Spring Water for Human Keratinocytes Differentiation

2021 ◽  
Vol 7 (2) ◽  
pp. 1-6
Author(s):  
Franck Juchaux ◽  
Keyword(s):  
Barrier Function ◽  
Skin Barrier ◽  
Human Keratinocytes ◽  
Spring Water ◽  
Keratinocyte Differentiation ◽  
Skin Barrier Function ◽  
Transglutaminase 1

Alterations of skin barrier function affect quality of life and there is a need to develop dermatological/cosmetic treatments to reinforce or restore it. Inspiring of Hailey-Hailey disease, in which barrier alteration is due to a mutation of a Calcium-transporting protein (ATP2C1), we focused on the role of minerals and more especially those contained in Saint-Gervais Mont Blanc (SGMB) spring water to reinforce barrier function. Objectives: Demonstrate the interest to enrich SGMB spring water with manganese to improve both keratinocytes differentiation and barrier function. Methods: Effects of treatments on the expression of ATP2C1 and on the expression of key markers in keratinocyte differentiation and barrier function were studied by gene expression analysis on keratinocytes monolayers and also by measuring the protein expression of transglutaminase 1 using in situ immunofluorescence and image analysis in keratinocytes monolayers. Results: SGMB spring water stimulates transcriptomic expression of key markers involved in keratinocytes differentiation and barrier function while manganese gluconate has no effect. Combination of both dramatically enhances keratinocytes differentiation, in a synergistic way, at both transcriptomic and protein level. None of treatments modulated ATP2C1 expression. Conclusion: These results highlight the interest to enrich SGMB spring water with manganese to boost keratinocytes differentiation and barrier function.

scholarly journals Accelerative Effect of Cinnamon Nanoparticles as well as HAMLET on Healing of Wounds Infected with MRSA in Diabetic Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Ramezani Ali ◽  
Najafpour Alireza ◽  
Farahpour Mohammad Reza ◽  
Mohammadi Rahim
Keyword(s):  
Diabetic Rats ◽  
Male Rats ◽  
Control Group ◽  
Wound Area ◽  
Sterile Saline ◽  
Area Reduction ◽  
Significant Difference ◽  
Healing Of Wounds ◽  
Polymerase Chain ◽  
Diabetic Wounds

Objective. The aim of the present study was to investigate the effect of cinnamon nanoparticles (CNPs) on healing of wounds infected with methicillin-resistant Staphylococcus aurous with human alpha-lactalbumin made lethal to tumor cells sensitization in diabetic rats. Methods. We included fifty diabetic male rats and divided them into 5 groups. There were 10 rats in each group as follows: CONTROL group: we did not infect the CONTROL group. The wound was only covered with sterile saline 0.9% solution (0.1 mL). INFCTD group: in this group, the wounds were infected with MRSA and covered with sterile saline 0.9% solution (0.1 mL). INFCTD-HMLT group: in this group, the wounds were infected with MRSA and HAMLET (100 μg). INFCTD-CNM group: in this group, the wounds were infected with MRSA and 0.1 mL CNPs (1 mg/mL) were applied topically to wounds. INFCTD-HMLT-CNM group: in this group, the wounds were infected with MRSA, HAMLET (100 μg), and 0.1 mL CNPs (1 mg/mL). Results. Bacteriology, wound area reduction measurements, biochemistry, histomorphometrical studies, hydroxyproline levels, and reverse transcription polymerase chain reaction for caspase-3, Bcl-2, and p53 showed significant difference between rats in the INFCTD-HMT-CNM group in comparison with other groups ( P < 0.05 ). Conclusions. Accelerated healing of diabetic wounds infected with MRSA showed that local application of cinnamon nanoparticles along with HAMLET sensitization on S. aureus-infected wound could be taken into consideration.

scholarly journals Aster glehniExtract Containing Caffeoylquinic Compounds Protects Human Keratinocytes through the TRPV4-PPARδ-AMPK Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-13
Author(s):  
Yong-Jik Lee ◽  
Yoo-Na Jang ◽  
Yoon-Mi Han ◽  
Hyun-Min Kim ◽  
Changbae Jin ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Sodium Dodecyl ◽  
Skin Barrier ◽  
Human Keratinocytes ◽  
Control Group ◽  
Hacat Cells ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Protein Levels ◽  
Ampk Pathway

Aster glehni(AG) has been used in cooking and as a medicine to treat various diseases for over hundreds of years in Korea. To speculate the protective effects of AG on skin barrier, we estimated the protein levels of biomarkers related to skin barrier protection in human keratinocytes, HaCaT cells treated with sodium dodecyl sulfate (SDS), or 2,4-dinitrochlorobenzene (DNCB). The protein levels for keratin, involucrin, defensin, tumor necrosis factor alpha (TNFα), peroxisome proliferator-activated receptor delta (PPARδ), 5′ adenosine monophosphate-activated protein kinase (AMPK), serine palmitoyltransferase long chain base subunit 2 (SPTLC2), and transient receptor potential cation channel subfamily V member 4 (TRPV4) were evaluated using western blotting or immunocytochemistry in HaCaT cells. AG extract increased the protein levels of PPARδ, phosphorylated AMPK, SPTLC2, keratin, involucrin, and defensin compared to the SDS or DNCB control group. However, TNFαexpression increased by SDS or DNCB was decreased with AG extract. The order of action of each regulatory biomarker in AG pathway was identified TRPV4→PPARδ→AMPK from antagonist and siRNA treatment studies. AG can ameliorate the injury of keratinocytes caused by SDS or DNCB through the sequential regulation of TRPV4→PPARδ→AMPK pathway.

scholarly journals In Vitro Effects of Dehydrotrametenolic Acid on Skin Barrier Function

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4583 ◽  
Author(s):  
Eunju Choi ◽  
Young-Gyu Kang ◽  
So-Hyeon Hwang ◽  
Jin Kyeong Kim ◽  
Yong Deog Hong ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Barrier Function ◽  
Skin Barrier ◽  
Keratinocyte Differentiation ◽  
Luciferase Reporter ◽  
Skin Barrier Function ◽  
Hacat Cells ◽  
Differentiation Markers ◽  
Triterpene Acid

Dehydrotrametenolic acid (DTA) is a lanostane-type triterpene acid isolated from Poria cocos Wolf (Polyporaceae). Several studies have reported the anti-inflammatory and antidiabetic effects of DTA; however, its effects on the skin are poorly understood. In this study, we investigated the effects of DTA on skin barrier function in vitro and its regulatory mechanism in human keratinocyte cell line HaCaT cells. DTA increased the microRNA (mRNA) expression of natural moisturizing factor-related genes, such as HAS-2, HAS-3, and AQP3 in HaCaT cells. DTA also upregulated the mRNA expression of various keratinocyte differentiation markers, including TGM-1, involucrin, and caspase-14. Moreover, the protein expression of HAS-2, HAS-3, and TGM-2 were significantly increased by DTA. To examine the regulatory mechanisms of DTA, Western blotting, luciferase-reporter assays, and RT-PCR were conducted. The phosphorylation of mitogen-activated protein kinases (MAPKs) and IκBα were increased in DTA-treated HaCaT cells. In addition, AP-1 and NF-κB transcriptional factors were dose-dependently activated by DTA. Taken together, our in vitro mechanism studies indicate that the regulatory effects of DTA on skin hydration and keratinocyte differentiation are mediated by the MAPK/AP-1 and IκBα/NF-κB pathways. In addition, DTA could be a promising ingredient in cosmetics for moisturizing and increased skin barrier function.

The Effect of Myrtus communis Aqueous Extract-Containing Gel on Wound Healing in Streptozotocin-Induced Diabetic Rats

2020 ◽  
Vol 17 ◽  
Author(s):  
Seyed-Ali Khodaie ◽  
Fatemeh Emadi ◽  
Mohsen Naseri ◽  
Mohammad Kamalinejad ◽  
Seyed Mohammad Riahi ◽  
...  
Keyword(s):  
Wound Healing ◽  
Aqueous Extract ◽  
Diabetic Rats ◽  
Control Group ◽  
Myrtus Communis ◽  
Full Thickness Excision ◽  
Medicinal Properties ◽  
Diabetic Wounds ◽  
Made In ◽  
Wound Tissue

Background: : The medicinal plant Myrtus communis L. (Myrtle) has been medicinal properties including antiinflammatory and wound healing in Persian Medicine. Objective: The objective of this study was to explore the wound healing potential of the local application of a gel containing aqueous extract of the plant berry in streptozotocin (STZ)-induced diabetic rats. Methods: Seven days after diabetes establishment, full-thickness excision skin wounds were made in normal and diabetic rats and treated groups received topical application of a gel containing 6% aqueous extract of myrtle berries for 3 weeks. The rate of wound healing and the level of epidermal and dermal maturation in the wound tissue were determined. Results: The results showed that after 3 and 7 days of wound injury, the gel significantly improved wound healing by accelerating epidermal and dermal maturation in diabetic rats with no significant effect in control group. However, the wounds of all groups almost completely healed after 3 weeks. Conclusion: These results demonstrate that aqueous extract of myrtle possesses a definite wound healing potential in diabetic condition. Our present findings may suggest the use of topical myrtle berries aqueous extract gel 6% to treat and manage intractable diabetic wounds.

scholarly journals Eucalyptus Citriodora Extract Regulates Cutaneous Homeostasis Including Immune Dysregulation and Skin Barrier Dysfunction Via the Modulation of Peroxisome Proliferator-Activated Receptor-β/δ (PPAR-β/δ) Pathway

2020 ◽  
Vol 4 (2) ◽  
pp. 23
Author(s):  
Takuhiro Yamada ◽  
Akihiro Aioi
Keyword(s):  
Mrna Expression ◽  
Skin Barrier ◽  
Immune Dysregulation ◽  
Keratinocyte Differentiation ◽  
Hacat Cells ◽  
Skin Disorders ◽  
Eucalyptus Citriodora ◽  
Barrier Dysfunction ◽  
Differentiation Markers ◽  
Transfected Cells

Perturbation of cutaneous homeostasis including immune dysregulation and skin barrier dysfunction evokes skin disorders. In this study, we examined the effect of Eucalyptus citriodora (Euc-c) extract on cytokine production, cell proliferation and cell differentiation in HaCaT cells to elucidate its influence on cutaneous homeostasis. Euc-c suppressed significantly LPS-induced IL-6 and TNF-a-induced IL-8 production from HaCaT cells. Conversely IL-1ra production was significantly enhanced by Euc-c. The expressions of IVL, CERS3 and CERS4, keratinocyte differentiation markers, were upregulated to 3.1, 2.8 and 2.7-fold respectively by Euc-c treatment, compared to the control, while the proliferation was downregulated. The lipid contents in Euc-c-treated cells tended to increase, compared with non-treated cells. To explore the underlying mechanism of these effect, we next performed siRNA experiments against PPAR-b/d. Euc-c enhanced PPAR-b/d mRNA expression to 3.25-fold, while PPAR-b/d mRNA expression in transfected cells was suppressed. The expressions of IVL, CERS3 and CERS4 in transfected cells were suppressed to 1.48, 0.82 and 0.72-fold respectively, concomitant with suppression of PPAR-b/d mRNA expression. These results indicated that Euc-c exerts anti-inflammatory effects and regulates keratinocyte differentiation via the modulation of PPAR-b/d pathway. Therefore, the application of Euc-c is expected to exert beneficial effect on skin disorders evoked by perturbation of skin homeostasis.

Different therapeutic effects between diabetic and non-diabetic adipose stem cells in diabetic wound healing

2021 ◽  
Vol 30 (Sup4) ◽  
pp. S14-S23
Author(s):  
Jia-Hong Gong ◽  
Jiao-Yun Dong ◽  
Ting Xie ◽  
Qingnan Zhao ◽  
Shu-Liang Lu
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Adipose Tissue ◽  
Cell Transplantation ◽  
Healing Process ◽  
Diabetic Rats ◽  
Therapeutic Effects ◽  
Wound Margin ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

Objective: This study aimed to investigate how adipose tissue-derived stem cells (ASCs) from diabetic and from non-diabetic rats affect wound healing in different microenvironments. Method: The two types of ASC-rich cells were distinguished by characteristic surface antigen detection. The ASC-rich cells were transplanted into the wounds of diabetic and non-diabetic rats. Wound healing rates were compared and the healing process in the wound margin sections was used to determine how ASC-rich cells affect wound healing in different microenvironments. Results: ASC density was decreased in diabetic rats. The generation time of ASC-rich cells from diabetic rats (d-ASC-rich cells) was longer than that of ASC-rich cells from non-diabetic rats. The number of pre-apoptotic cells in the third generation (passage 3) of d-ASC-rich cells was higher than that among the ASC-rich cells from non-diabetic rats. CD31 and CD34 expression was higher in d-ASC-rich cells than in ASC-rich cells from non-diabetic rats, whereas CD44 and CD105 expression was lower than that in ASC-rich cells from non-diabetic rats. Transplantation of ASC-rich cells from non-diabetic rats promoted wound healing in both non-diabetic and diabetic rats. In contrast, d-ASC-rich cells and enriched nuclear cells only promoted wound healing in non-diabetic rats. ASC-rich cell transplantation promoted greater tissue regeneration than d-ASC-rich cell transplantation. Conclusion: ASC-rich cells promoted wound healing in diabetic and non-diabetic rats. ASC density was lower in the adipose tissue of diabetic rats compared with non-diabetic rats. d-ASC-rich cells did not promote wound healing in diabetic rats, suggesting that caution is warranted regarding the clinical use of diabetic adipose stem cell transplantation for the treatment of diabetic wounds.

Anti-diabetic activity of diphenhydramine in diabetic rats

2020 ◽  
Vol 11 (4) ◽  
pp. 5067-5070
Author(s):  
Pang Jyh Chayng ◽  
Nurul Ain ◽  
Kaswandi Md Ambia ◽  
Rahim Md Noah
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Fasting Blood Glucose ◽  
Insulin Level ◽  
Diabetic Rats ◽  
Group Iv ◽  
Diabetic Rat ◽  
Control Group ◽  
Group I

The purpose of this project is to study the anti-diabetic effect of on a diabetic rat model. A total of Twenty male Sprague rats were used and it randomly distributed into four groups which are Group I: , Group II: negative control, Group III: and Group IV: and . In diabetic model were induced with via injection at the dosage of 65mg/kg. and FBG (Fasting Blood Glucose) level of diabetic rats were assessed every three days. Blood was collected via cardiac puncture at day 21 after the induction of treatment. Insulin level of the rats was assessed with the Mercodia Rat Insulin ELISA kit. FBG level of group I (12.16 ±3.96, p&lt;0.05) and group IV (11.34 ±3.67, p&lt;0.05) were significantly decreased. Meanwhile, the for all rats did not show any significant increase. However, the insulin level was escalated in group IV (0.74+0.25, p&lt;0.05) significantly. The present study shows that the and the combination of and lowered blood glucose level and enhanced insulin secretion.

Sign in / Sign up

Export Citation Format

Share Document