scholarly journals Ferulic Acid Induces Keratin 6α via Inhibition of Nuclear β-Catenin Accumulation and Activation of Nrf2 in Wound-Induced Inflammation

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 459
Author(s):  
Kang-Hoon Kim ◽  
Ji Hoon Jung ◽  
Won-Seok Chung ◽  
Chang-Hun Lee ◽  
Hyeung-Jin Jang
Keyword(s):  
Wound Healing ◽  
Ferulic Acid ◽  
Wound Closure ◽  
Secondary Infection ◽  
Bioactive Compound ◽  
Explant Culture ◽  
Negative Regulator ◽  
Epidermal Keratinocytes ◽  
Related Factor ◽  
Human Epidermal Keratinocytes

Injured tissue triggers complex interactions through biological process associated with keratins. Rapid recovery is most important for protection against secondary infection and inflammatory pain. For rapid wound healing with minimal pain and side effects, shilajit has been used as an ayurvedic medicine. However, the mechanisms of rapid wound closure are unknown. Here, we found that shilajit induced wound closure in an acute wound model and induced migration in skin explant cultures through evaluation of transcriptomics via microarray testing. In addition, ferulic acid (FA), as a bioactive compound, induced migration via modulation of keratin 6α (K6α) and inhibition of β-catenin in primary keratinocytes of skin explant culture and injured full-thickness skin, because accumulation of β-catenin into the nucleus acts as a negative regulator and disturbs migration in human epidermal keratinocytes. Furthermore, FA alleviated wound-induced inflammation via activation of nuclear factor erythroid-2-related factor 2 (Nrf2) at the wound edge. These findings show that FA is a novel therapeutic agent for wound healing that acts via inhibition of β-catenin in keratinocytes and by activation of Nrf2 in wound-induced inflammation.

scholarly journals Abalone Collagen Extracts Potentiate Stem Cell Properties of Human Epidermal Keratinocytes

Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 424
Author(s):  
Sajee Thaweekitphathanaphakdee ◽  
Pithi Chanvorachote ◽  
Sagaw Prateepchinda ◽  
Mattaka Khongkow ◽  
Apirada Sucontphunt
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Stem Cell ◽  
Cell Migration ◽  
Expression Level ◽  
Epidermal Keratinocytes ◽  
Stem Cell Markers ◽  
Spheroid Formation ◽  
Human Epidermal Keratinocytes ◽  
Cell Markers

Stem cell activities in human tissues are critical for tissue integrity and function. Maintaining keratinocyte stem cells (KSCs) stemness helps sustain healthy skin by supporting keratinocyte renewal, involving the formation of epidermal barriers. In this study, abalone collagen (AC) extracts with molecular weights of 3 kDa (AC 1) and 300 kDa (AC 2) were compared to the epidermal growth factor (EGF) for their effects on cell proliferation, cell migration (wound healing), spheroid formation, and the expression level of stem cell markers on human keratinocytes (HaCaT cells). Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell proliferation was quantified by ATP and DNA content analysis and Sulforhodamine B (SRB) assays. Cell migration assay was determined using the scratch wound healing test. Spheroid formation was evaluated and the expression level of stem cell markers was investigated by western blot analysis. The results showed that AC 1 at the concentration of 100 µg/mL could stimulate HaCaT cell proliferation, migration, spheroid formation, and the expression level of stem cell markers (keratin 19, β-catenin, ALDH1A1) compared to the control. In conclusion, a smaller molecular weight of abalone collagen extract exhibits a better effect on keratinocytes proliferation, migration, and stemness, which could be a potential active ingredient in cosmeceutical products.

Ras‐induced spreading and wound closure in human epidermal keratinocytes

2005 ◽  
Vol 19 (13) ◽  
pp. 1836-1838 ◽  
Author(s):  
Michael Tscharntke ◽  
Ruth Pofahl ◽  
Thomas Krieg ◽  
Ingo Haase
Keyword(s):  
Wound Closure ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes

scholarly journals Redox for Repair: Cold Physical Plasmas and Nrf2 Signaling Promoting Wound Healing

Antioxidants ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 146 ◽  
Author(s):  
Anke Schmidt ◽  
Sander Bekeschus
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Chronic Wounds ◽  
Health Care Systems ◽  
Molecular Switches ◽  
Dermal Fibroblasts ◽  
Tissue Response ◽  
Related Factor ◽  
Plasma Effects ◽  
Care Systems

Chronic wounds and ulcers are major public health threats. Being a substantial burden for patients and health care systems alike, better understanding of wound pathophysiology and new avenues in the therapy of chronic wounds are urgently needed. Cold physical plasmas are particularly effective in promoting wound closure, irrespective of its etiology. These partially ionized gases deliver a therapeutic cocktail of reactive oxygen and nitrogen species safely at body temperature and without genotoxic side effects. This field of plasma medicine reanimates the idea of redox repair in physiological healing. This review compiles previous findings of plasma effects in wound healing. It discusses new links between plasma treatment of cells and tissues, and the perception and intracellular translation of plasma-derived reactive species via redox signaling pathways. Specifically, (i) molecular switches governing redox-mediated tissue response; (ii) the activation of the nuclear E2-related factor (Nrf2) signaling, together with antioxidative and immunomodulatory responses; and (iii) the stabilization of the scaffolding function and actin network in dermal fibroblasts are emphasized in the light of wound healing.

scholarly journals Human Epidermal Keratinocytes Are a Source of Tenascin-C during Wound Healing

1997 ◽  
Vol 108 (5) ◽  
pp. 776-783 ◽  
Author(s):  
Mieke Latijnhouwers ◽  
Mieke Bergers ◽  
Maria Ponec ◽  
Henri Dijkman ◽  
Monique Andriessen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Tenascin C

scholarly journals S100C/A11 is a key mediator of Ca2+-induced growth inhibition of human epidermal keratinocytes

2003 ◽  
Vol 163 (4) ◽  
pp. 825-835 ◽  
Author(s):  
Masakiyo Sakaguchi ◽  
Masahiro Miyazaki ◽  
Mikiro Takaishi ◽  
Yoshihiko Sakaguchi ◽  
Eiichi Makino ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Growth Regulation ◽  
Nuclear Translocation ◽  
Basal Layer ◽  
Human Keratinocytes ◽  
Negative Regulator ◽  
Epidermal Keratinocytes ◽  
Proliferating Cells ◽  
Human Epidermal Keratinocytes

An increase in extracellular Ca2+ induces growth arrest and differentiation of human keratinocytes in culture. We examined possible involvement of S100C/A11 in this growth regulation. On exposure of the cells to high Ca2+, S100C/A11 was specifically phosphorylated at 10Thr and 94Ser. Phosphorylation facilitated the binding of S100C/A11 to nucleolin, resulting in nuclear translocation of S100C/A11. In nuclei, S100C/A11 liberated Sp1/3 from nucleolin. The resulting free Sp1/3 transcriptionally activated p21CIP1/WAF1, a representative negative regulator of cell growth. Introduction of anti-S100C/A11 antibody into the cells largely abolished the growth inhibition induced by Ca2+ and the induction of p21CIP1/WAF1. In the human epidermis, S100C/A11 was detected in nuclei of differentiating cells in the suprabasal layers, but not in nuclei of proliferating cells in the basal layer. These results indicate that S100C/A11 is a key mediator of the Ca2+-induced growth inhibition of human keratinocytes in culture, and that it may be possibly involved in the growth regulation in vivo as well.

scholarly journals A novel Nrf2 activator from microbial transformation inhibits radiation-induced dermatitis in mice

2016 ◽  
Vol 57 (5) ◽  
pp. 567-571 ◽  
Author(s):  
Yasuhiro Nakagami ◽  
Kayoko Masuda
Keyword(s):  
Microbial Transformation ◽  
Radiation Dermatitis ◽  
Epidermal Keratinocytes ◽  
Related Factor ◽  
Human Epidermal Keratinocytes ◽  
Potential Efficacy ◽  
Patients At Risk ◽  
Radiation Induced ◽  
Normal Human ◽  
Nrf2 Activator

Abstract Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that regulates many antioxidants, and we have recently succeeded in obtaining a novel Nrf2 activator, RS9, from microbial transformation. RS9 is categorized as a triterpenoid, and well-known triterpenoids such as RTA 402 (bardoxolone methyl) and RTA 408 have been tested in clinical trials. RTA 408 lotion is currently being tested in patients at risk for radiation dermatitis. This prompted us to study the profiles of RS9 in the skin. All the above triterpenoids increased the level of an Nrf2-targeted gene, NADPH:quinone oxidoreductase-1, in normal human epidermal keratinocytes. Among them, the activity of RS9 was prominent; furthermore, the cellular toxicity was less compared with RTA compounds. BALB/c mice were irradiated with 30 Gy/day on Day 0, and compounds were topically applied on the back once daily from Day 1 to Day 30. Dermatitis scores peaked on Day 18, with a score of 2.6 in vehicle-treated mice, and topical applications of 0.1% RTA 402, RTA 408 and RS9 reduced the scores to 1.8, 2.0 and 1.4, respectively. Moreover, the percentage of animals with scores ≥2 was analyzed, and 0.1% RS9 suppressed the percentage from 100% to 47%. These results imply that RS9 has potential efficacy for treating radiation dermatitis.

scholarly journals A Novel Substance P-Based Hydrogel for Increased Wound Healing Efficiency

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2215 ◽  
Author(s):  
Da Kim ◽  
Ji Jang ◽  
Song Jang ◽  
Jungsun Lee
Keyword(s):  
Wound Healing ◽  
Substance P ◽  
Dermal Fibroblasts ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
In Vivo Experiments ◽  
And Migration ◽  
Proliferation And Migration

The neuropeptide substance P (SP) is known to stimulate wound healing by regulating the production of relevant cytokines as well as cell proliferation and migration. However, the therapeutic application of SP is limited by its low stability under biological conditions and oxidation during purification, formulation, and storage. To address this problem, we developed a novel formulation of SP as an SP gel, and investigated its wound healing activity both in vitro and in vivo. SP in SP gel was stable at various temperatures for up to 4 weeks. In vitro, SP gel exhibited more potential as a candidate wound-healing agent than SP alone, as evidenced by the observed increases in the proliferation and migration of human epidermal keratinocytes and human dermal fibroblasts. In vivo experiments showed that SP gel treatment enhanced the healing of full-thickness wounds in mice as compared to SP alone. These results demonstrate the benefits of SP gel as a promising topical agent for wound treatment.

scholarly journals Interleukin 6 Function in the Skin and Isolated Keratinocytes Is Modulated by Hyperglycemia

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Eric G. Lee ◽  
Lerin R. Luckett-Chastain ◽  
Kaitlin N. Calhoun ◽  
Benjamin Frempah ◽  
Anja Bastian ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Interleukin 6 ◽  
Wound Closure ◽  
Cultured Cells ◽  
Health Care Cost ◽  
Epidermal Keratinocytes ◽  
Type I ◽  
Primary Mouse ◽  
Time Point

Diabetes currently affects over twenty-five million Americans. Annual health care cost of diabetes exceeds $254 billion and is associated with a distinct set of diabetic complications that include delayed wound healing and diabetic ulcers. Interleukin 6 (IL-6) plays an important role in wound healing and is known to be elevated in the serum of both type I and type II diabetes patients. This study assesses the expression and function of IL-6 in the hyperglycemic epidermis and keratinocyte culture. Streptozotocin-treated mice were wounded six weeks after induction of hyperglycemia. Wound closure, protein, and mRNA expression were assessed up to 13 days of postwounding. Wound closure was delayed 4-5 days in hyperglycemic animals. Hyperglycemic wounds displayed greater IL-6 and IL-6Rα protein expression at 1, 7, and 10 days of postwounding compared to euglycemic control. However, IL-6Rα mRNA expression was reduced at all time points beyond day 1, while IL-6 mRNA expression did not significantly differ at any time point. SOCS3 mRNA expression was higher in the hyperglycemic skin at every time point. Imaging of fluorescent immunohistology also revealed significantly lower expression of SOCS3, but higher nuclear pSTAT3 in the epidermis of the hyperglycemic skin. Primary mouse keratinocytes cultured in high glucose for 7 days displayed 2-fold higher IL-6Rα mRNA and higher rmIL-6-induced nuclear pSTAT3, but lower SOCS3 basal levels compared to normal glucose-cultured cells. Thus, it appears that delayed diabetic skin wound healing is associated with increased induction and expression of IL-6 and its receptor, but its function in epidermal keratinocytes may be impaired.

scholarly journals 12-hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor

2014 ◽  
Vol 211 (6) ◽  
pp. 1063-1078 ◽  
Author(s):  
Min Liu ◽  
Kazuko Saeki ◽  
Takehiko Matsunobu ◽  
Toshiaki Okuno ◽  
Tomoaki Koga ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Cultured Cells ◽  
Leukotriene B4 ◽  
Epidermal Keratinocytes ◽  
Skin Wound Healing ◽  
Wound Fluid ◽  
Deficient Mice

Leukotriene B4 (LTB4) receptor type 2 (BLT2) is a G protein–coupled receptor (GPCR) for 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) and LTB4. Despite the well-defined proinflammatory roles of BLT1, the in vivo functions of BLT2 remain elusive. As mouse BLT2 is highly expressed in epidermal keratinocytes, we investigated the role of the 12-HHT/BLT2 axis in skin wound healing processes. 12-HHT accumulated in the wound fluid in mice, and BLT2-deficient mice exhibited impaired re-epithelialization and delayed wound closure after skin punching. Aspirin administration reduced 12-HHT production and resulted in delayed wound closure in wild-type mice, which was abrogated in BLT2-deficient mice. In vitro scratch assay using primary keratinocytes and a keratinocyte cell line also showed that the 12-HHT/BLT2 axis accelerated wound closure through the production of tumor necrosis factor α (TNF) and matrix metalloproteinases (MMPs). A synthetic BLT2 agonist accelerated wound closure in cultured cells as well as in C57BL/6J and diabetic mice. These results identify a novel mechanism underlying the action of the 12-HHT/BLT2 axis in epidermal keratinocytes and accordingly suggest the use of BLT2 agonists as therapeutic agents to accelerate wound healing, particularly for intractable wounds, such as diabetic ulcers.

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