19 Effect of glucosylceramide synthase inhibitor on growth and migration of cultured human keratinocytes

AbstractObjectivesWound healing is a complex process with a sequence of restoring and inhibition events such as cell proliferation, differentiation, migration as well as adhesion. Mesenchymal stem cells (MSC) derived conditioned medium (CM) has potent therapeutic functions and promotes cell proliferation, anti-oxidant, immunosuppressive, and anti-apoptotic effects. The main aim of this research is to study the role of human umbilical cord-mesenchymal stem cells (UC-MSCs) derived CM in stimulating the proliferation of human keratinocytes (HaCaT).MethodsFirstly, MSC were isolated from human umbilical cords (UC) and the cells were then cultured in proliferative medium. We prepared and collected the CM after 72 h. Morphological changes were observed after the treatment of HaCaT cells with CM. To validate the findings, proliferation rate, clonal efficiency and also gene expression studies were performed.ResultsIncreased proliferation rate was observed and confirmed with the expression of Proliferating Cell Nuclear Antigen (PCNA) after treatment with HaCaT cells. Cell-cell strap formation was also observed when HaCaT cells were treated with CM for a period of 5–6 days which was confirmed by the increased expression of Collagen Type 1 Alpha 1 chain (Col1A1).ConclusionsOur results from present study depicts that the secretory components in the CM might play a significant role by interacting with keratinocytes to promote proliferation and migration. Thus, the CM stimulates cellular proliferation, epithelialization and migration of skin cells which might be the future promising application in wound healing.

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Achyrocline satureioides (Lam.) DC (Asteraceae) Extract-Loaded Nanoemulsions as a Promising Topical Wound Healing Delivery System: In Vitro Assessments in Human Keratinocytes (HaCaT) and HET-CAM Irritant Potential

Pharmaceutics ◽

10.3390/pharmaceutics13081241 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1241

Author(s):

Lucélia Albarello Balestrin ◽

Tainá Kreutz ◽

Flávia Nathiely Silveira Fachel ◽

Juliana Bidone ◽

Nicolly Espindola Gelsleichter ◽

...

Keyword(s):

Wound Healing ◽

Hacat Cell ◽

Chorioallantoic Membrane ◽

Human Keratinocytes ◽

Scratch Assay ◽

Hen’S Egg ◽

And Migration ◽

Achyrocline Satureioides ◽

Proliferation And Migration

Achyrocline satureioides (Lam.) DC Asteraceae extracts (ASEs) have been investigated for the treatment of various skin disorders. This study reports the effects of ASE-loaded nanoemulsions (NEASE) on the cellular viability, death by necrosis, and migration of immortalized human keratinocytes (HaCaT cell line), as well as the irritant potential through the hen’s egg chorioallantoic membrane test (HET-CAM). NEASE exhibited a polydispersity index above 0.12, with a droplet size of 300 nm, ζ-potential of −40 mV, and content of flavonoids close to 1 mg/mL. No cytotoxicity of the ASE was observed on HaCaT by MTT assay (up to 10 µg/mL). A significant increase of HaCaT viability was observed to NEASE (up to 5 μg/mL of flavonoids), compared to treatment with the ASE. The necrosis death evaluation demonstrated that only NEASE did not lead to cell death at all the tested concentrations. The scratch assay demonstrated that NEASE was able to increase the cell migration at low flavonoid concentrations. Finally, the HET-CAM test proved the non-irritative potential of NEASE. Overall, the results indicate the potential of the proposed formulations for topical use in wound healing, in view of their promising effects on proliferation and migration in keratinocytes, combined with an indication of the absence of cytotoxicity and non-irritating potential.

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Eliglustat tartrate, a prototypic glucosylceramide synthase inhibitor

Expert Review of Endocrinology & Metabolism ◽

10.1586/17446651.2013.846213 ◽

2013 ◽

Vol 8 (6) ◽

pp. 491-504 ◽

Cited By ~ 4

Author(s):

James A Shayman

Keyword(s):

Glucosylceramide Synthase ◽

Synthase Inhibitor

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Glucosylceramide Synthase Inhibitor Inhibits the Action of Nerve Growth Factor in PC12 Cells

Journal of Biological Chemistry ◽

10.1074/jbc.273.40.26001 ◽

1998 ◽

Vol 273 (40) ◽

pp. 26001-26007 ◽

Cited By ~ 61

Author(s):

Tatsuro Mutoh ◽

Akira Tokuda ◽

Jin-ichi Inokuchi ◽

Masaru Kuriyama

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Pc12 Cells ◽

Glucosylceramide Synthase ◽

Nerve Growth ◽

Synthase Inhibitor

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Loliolide Presents Antiapoptosis and Antiscratching Effects in Human Keratinocytes

International Journal of Molecular Sciences ◽

10.3390/ijms20030651 ◽

2019 ◽

Vol 20 (3) ◽

pp. 651 ◽

Cited By ~ 5

Author(s):

Sang Park ◽

Dong Kim ◽

Sunggyu Kim ◽

Laura Lorz ◽

Eunju Choi ◽

...

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Signaling Pathway ◽

Keratinocyte Growth Factor ◽

Growth Factor Receptor ◽

Ethanol Extract ◽

Human Keratinocytes ◽

Freshwater Algae ◽

And Migration ◽

Induced Apoptosis

Loliolide is a monoterpenoid hydroxylactone present in freshwater algae that has anti-inflammatory and antiaging activity; however, its effects on ultraviolet-damaged skin have yet to be elucidated. This study investigated the antiapoptosis and wound-healing effects of loliolide using HaCaT cells (a human keratinocyte cell line). Loliolide inhibited the expression of reactive oxygen species (ROS) induced by ultraviolet radiation as well as wrinkle formation-related matrix metalloproteinase genes and increased the expression of the damage repair-related gene SIRT1. The apoptosis signaling pathway was confirmed by Western blot analysis, which showed that loliolide was able to reduce the expression of caspases 3, 8, and 9, which are related to ROS-induced apoptosis. In addition, Western blotting, reverse-transcription polymerase chain reaction (PCR), and real-time PCR analyses showed that loliolide enhanced the expression of the epidermal growth factor receptor signaling pathway (PI3K, AKT) and migration factors, such as K6, K16, and K17; keratinocyte growth factor; and inflammatory cytokines, such as interleukin (IL)-1, IL-17, and IL-22 expressed during the cellular scratching process, suggesting a putative wound-healing ability. Because of the antiapoptosis and antiscratching effects on skin of both loliolide and loliolide-rich Prasiola japonica ethanol extract, we consider the former to be an important compound used in the cosmeceutical industry.

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