Effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor and low-density lipoprotein on proliferation and migration of keratinocytes

El-latif, Mostafa I. Abd; Murota, Hiroyuki; Terao, Mineko; Katayama, Ichiro

doi:10.1111/j.1365-2133.2010.09694.x

Cited by 14 publications

(9 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Copyright © 2021 IR Research Publication -All Rights Reserved Cholesterol carrier proteins play important roles in delivering the required cholesterol needed for the cell. Previous studies have shown that cholesterol improves the proliferation and migration of keratinocytes (10). In the present work, we have examined the role of LDL and pitavastatin on migration and cholesterol-mediated protein expression in fibroblasts.…”

Section: Discussionmentioning

confidence: 94%

“…Low-density lipoprotein (LDL) is associated with cholesterol deposition in peripheral vessels and plaque formation, resulting in a high risk for atherosclerosis and heart disease (15,16), and elevated LDL is a common reason for statin therapy. We chose pitavastatin in this study as it was shown to upregulate LDLr in cultured keratinocytes as well as mouse epidermis (10).…”

Section: Discussionmentioning

confidence: 99%

“…Statins have been shown to improve wound healing processes in both animal and human trials (4,9). The ability of pitavastatin to upregulate LDLr in normal human keratinocytes and HaCaT cells was confirmed by El-Latif et al (10). Their study also showed pitavastatin increased proliferation in keratinocytes, but not on their ability to migrate.…”

Section: Introductionmentioning

confidence: 91%

See 2 more Smart Citations

The effects of LDL cholesterol and pitavastatin treatment on fibroblast migration, SREBP-2, and LDLr expression

Telgenhoff

Prajapati

2022

biolsciences

View full text Add to dashboard Cite

Most non-healing wounds show a lack of cell migration contributing to chronic inflammation and infection. Cholesterol levels in the blood may have an impact on cell migration, as migrating cells demonstrate a need for cholesterol in order to synthesize additional cell membranes. Statins are a popular drug used for lowering blood cholesterol by competitive inhibition of HMG CoA reductase, a pivotal step in the cholesterol synthesis pathway. In this study, we examined the effects of low-density lipoprotein (LDL) and statin treatment on fibroblasts in vitro. A cholesterol ELISA was utilized to examine cholesterol levels in cultured fibroblasts following treatment with pitavastatin or LDL. A scratch-test assay was performed to examine fibroblast migration following treatment in addition to the MTT cell proliferation assay. Western blot analysis was used to examine the cholesterol signalling protein SREBP-2 and LDLr expression in treated cells. LDL treatment enhanced cell proliferation and migration, while both were inhibited by pitavastatin. Pitavastatin increased both SREBP-2 and LDLr expression in treated cells compared to LDL and vehicle control treatments. These results indicate pitavastatin inhibits cell migration and the cellular response is to increase cholesterol levels to make up for the inhibition of cholesterol synthesis though the mevalonate pathway. This could have significant effects on cell migration and wound healing in vivo for patients with inhibited wound healing responses on statin therapy.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

See 1 more Smart Citation

The effects of LDL cholesterol and pitavastatin treatment on fibroblast migration, SREBP-2, and LDLr expression

Telgenhoff

Prajapati

2022

biolsciences

View full text Add to dashboard Cite

show abstract

“…Effective cholesterol homeostasis in keratinocytes and dermal fibroblasts is needed to sustain the integrity of cutaneous permeability barrier function [41][42][43][44] and to provide one of the key membrane components needed for cellular proliferation and migration [45][46][47][48]. Here, cholesterol efflux was used primarily as confirmation of cellular responsiveness to HDL (Figure 2), but some interesting findings emerge, most notably that efflux from neonatal dermal fibroblasts was lower than that observed in adult dermal fibroblasts and keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

Homo Sapiens (Hsa)-microRNA (miR)-6727-5p Contributes to the Impact of High-Density Lipoproteins on Fibroblast Wound Healing In Vitro

Bastaki¹,

Tarlton²,

Lightbody³

et al. 2022

Membranes

View full text Add to dashboard Cite

Chronic, non-healing wounds are a significant cause of global morbidity and mortality, and strategies to improve delayed wound closure represent an unmet clinical need. High-density lipoproteins (HDL) can enhance wound healing, but exploitation of this finding is challenging due to the complexity and instability of these heterogeneous lipoproteins. The responsiveness of primary human neonatal keratinocytes, and neonatal and human dermal fibroblasts (HDF) to HDL was confirmed by cholesterol efflux, but promotion of ‘scrape’ wound healing occurred only in primary human neonatal (HDFn) and adult fibroblasts (HDFa). Treatment of human fibroblasts with HDL induced multiple changes in the expression of small non-coding microRNA sequences, determined by microchip array, including hsa-miR-6727-5p. Intriguingly, levels of hsa-miR-6727-5p increased in HDFn, but decreased in HDFa, after exposure to HDL. Delivery of a hsa-miR-6727-5p mimic elicited repression of different target genes in HDFn (ZNF584) and HDFa (EDEM3, KRAS), and promoted wound closure in HDFn. By contrast, a hsa-miR-6727-5p inhibitor promoted wound closure in HDFa. We conclude that HDL treatment exerts distinct effects on the expression of hsa-miR-6727-5p in neonatal and adult fibroblasts, and that this is a sequence which plays differential roles in wound healing in these cell types, but cannot replicate the myriad effects of HDL.

show abstract

“…Earlier studies indicate that the low-density-lipoprotein (LDL) receptor was expressed on the epidermis [ 22 , 23 ]. The LDL receptor was expressed at a higher level in the psoriasis skin than in the normal skin [ 24 , 25 ]. Human low-density lipoprotein is the major lipid protein complex in the blood for the transport of lipids throughout the body.…”

Section: Discussionmentioning

confidence: 99%

Oxidized Low-Density Lipoprotein-Deteriorated Psoriasis Is Associated with the Upregulation of Lox-1 Receptor and Il-23 Expression In Vivo and In Vitro

Shih

Huang

Wang

et al. 2018

IJMS

View full text Add to dashboard Cite

Psoriasis is a chronic inflammatory skin disease. Even though scientists predict that abnormalities in lipid metabolism play an important role in the pathogenesis of psoriasis, the actual underlying mechanisms are still unclear. Therefore, understanding the possible relationship between mechanisms of the occurrence of psoriasis and dyslipidemia is an important issue that may lead to the development of effective therapies. Under this principle, we investigated the influences of hyperlipidemia in imiquimod (IMQ)-induced psoriasis-like B6.129S2-Apoetm1Unc/J mice and oxidized low-density lipoprotein (oxLDL) in tumor necrosis factor (TNF)-α-stimulated Hacat cells. In our study, we showed that a high-cholesterol diet aggravated psoriasis-like phenomena in IMQ-treated B6.129S2-Apoetm1Unc/J mice. In vitro analysis showed that oxLDL increased keratinocyte migration and lectin-type oxLDL receptor 1 (LOX-1) expression. Evidence suggested that interleukin (IL)-23 was a main cytokine in the pathogenesis of psoriasis. High-cholesterol diet aggravated IL-23 expression in IMQ-treated B6.129S2-Apoetm1Unc/J mice, and oxLDL induced IL-23 expression mediated by LOX-1 in TNF-α-stimulated Hacat cells. Therefore, it will be interesting to investigate the factors for the oxLDL induction of LOX-1 in psoriasis. LOX-1 receptor expression may be another novel treatment option for psoriasis and might represent the most promising strategy.

show abstract

Effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor and low-density lipoprotein on proliferation and migration of keratinocytes

Abstract: Pitavastatin significantly upregulates LDLR in both NHKs and C57BL6 mouse skin, resulting in increased keratinocyte proliferation. LXRbeta may be involved in the pitavastatin-induced keratinocyte proliferation.

Cited by 14 publications

References 18 publications

The effects of LDL cholesterol and pitavastatin treatment on fibroblast migration, SREBP-2, and LDLr expression

The effects of LDL cholesterol and pitavastatin treatment on fibroblast migration, SREBP-2, and LDLr expression

Homo Sapiens (Hsa)-microRNA (miR)-6727-5p Contributes to the Impact of High-Density Lipoproteins on Fibroblast Wound Healing In Vitro

Oxidized Low-Density Lipoprotein-Deteriorated Psoriasis Is Associated with the Upregulation of Lox-1 Receptor and Il-23 Expression In Vivo and In Vitro

Contact Info

Product

Resources

About