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Molecular signature of pigment spots on the skin, associated with extracellular matrix organization

An external matrix, skin technology, applied in the field of pigmentation and the treatment of these pigmentations, can solve the problems of molecular imbalance or dysfunction, and no discussion of pigmentation mechanism dysfunction and other problems

Inactive Publication Date: 2014-03-05
LOREAL SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, various studies have not discussed the mechanisms underlying the pigmented appearance or the general dysfunction
[0019] There is no reliable data in the prior art indicating molecular dysregulation or dysfunction in this type of pigmentation disorder other than those closely associated with melanocytes and melanogenesis

Method used

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  • Molecular signature of pigment spots on the skin, associated with extracellular matrix organization
  • Molecular signature of pigment spots on the skin, associated with extracellular matrix organization
  • Molecular signature of pigment spots on the skin, associated with extracellular matrix organization

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0200] Example 1: Transcription Studies

[0201] Comparative study of gene expression levels in solar lentigo (LS) damaged skin and adjacent undamaged skin (US).

[0202] The aim of this study was to identify relevant, reproducible and significant markers that reflect the changes associated with solar lentigo formation in order to use them as targets for effective treatment or as a tool for analyzing the efficacy of a given treatment. landmark.

[0203] Briefly, 15 female volunteers were recruited to participate in a "genome-wide" transcriptome study (Array, Inc., USA). For each volunteer, a solar lentigo type lesion was diagnosed on the back of his hand, and this solar lentigo diagnosis was further confirmed by epidermal luminescence microscopy. This check is for:

[0204] 1) Identify lesions (solar lentigo specific) using criteria at the dermal-epidermal junction ("fingerprints") to differentiate lentigo (lack of fingerprints, uniform pigmentation, and moth-eaten border...

Embodiment 2

[0221] Example 2: Materials and methods

[0222] Fifteen female volunteers with phenotypes II-IV, aged between 50 and 70 years, were selected. Their solar lentigines on the dorsum of the hands were at least 3 mm in size. They were characterized by epiluminescence microscopy. Various advantages of characterization by epiluminescence microscopy have been indicated in Example 1.

[0223] Two 3 mm diameter biopsies were taken from one hand of each patient. For each volunteer, one biopsy corresponded to the solar lentigines lesion (LS) and the other corresponded to the other adjacent undamaged skin (US) (again confirmed by epidermal luminescence microscopy).

[0224] 3mm biopsy sections were sampled and placed in RNAlater (Qiagen cat. 76106) at 4°C for 16 to 24 hours. The next day, samples were placed at -20°C pending the homogenization and extraction steps. After thawing, samples were minced with a scalpel to facilitate homogenization prior to transfer to lysis buffer.

[...

Embodiment 3

[0243] Embodiment 3: Regulator:

[0244] There are compounds known to modulate protein dysregulation in lentigo. The following can be used as extracellular matrix gene / protein families:

[0245] - Fibrates including fenofibrate, for example to reduce the expression of SMAD3,

[0246] - alkaloids including oxymatrine, which reduces SMAD3, or polyphenols, such as salvianolic acid B, which reduces the expression of SMAD3 and TGFBR2,

[0247] - Natural extracts, especially herbal medicines such as Wenpi Decoction and Wuling Powder extract, which can reduce the expression of SMAD3,

[0248] - compounds of the imidazole family, which are antagonists of TGF-βR1, such as SB-431542, which reduces the expression of SMAD3,

[0249] - certain miRNAs, in particular miR183 and miR29b, which reduce the expression of ITGB1,

[0250] - inhibitors of urokinase-type plasminogen activators (uPA), such as p-aminobenzamidine or B428 4-substituted benzo[b]thiophene-2-carboxamidines, which redu...

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Abstract

The present invention relates to a molecular signature of pigment spots on the skin, comprising the MXRA5, LYZ, CTSL2, PLAU, TIMP1, EFEMP1, ECM1, ASPN, HS3ST6, PAPLN, CHSY1 and FLRT2 genes, and various applications of this signature. The invention relates in particular to a method for characterizing an apparent or suspected pigment spot in a human being, which comprises comparison of the levels of expression, in samples of skin taken from said spot and of non-lesioned adjacent skin, of at least one dermal gene related to matrix remodelling or to the extracellular proteoglycan and glycoprotein components thereof, chosen from the list consisting of the MXRA5, LYZ, CTSL2, PLAU, TIMP1, EFEMP1, ECM1, ASPN, HS3ST6, PAPLN, CHSY1 and FLRT2 genes. The invention also relates to methods for evaluating the efficacy of a treatment for pigment spots, to cosmetic and therapeutic methods for treating pigment spots, and also to various modulators of said genes and the use thereof.

Description

technical field [0001] The present invention relates to the field of cosmetics and is related to the skin. More generally, it concerns the characterization of pigmented spots on the skin and the treatment of these spots. Background technique [0002] Skin color is mainly due to pigments and melanin in the epidermis. Melanin is synthesized by specific dendritic cells located in the basal layer of the epidermis, known as melanocytes. Melanogenesis occurs in the organelle, melanin-filled melanosomes, which are transferred by dendritic cells to adjacent epidermal cells, keratinocytes. Skin tone or constitutive pigmentation varies among individuals in terms of the total amount of melanin produced and the chemical nature of melanin. Melanin is a macromolecule formed of tyrosine (eumelanin) or tyrosine and cysteine ​​(melatonin). The synthesis mechanism is mainly using tyrosinase and tyrosinase-related protein (Tyrp-1). Pigmentation of the skin is a natural reaction to exposur...

Claims

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Application Information

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IPC IPC(8): A61K8/60C12Q1/68A61Q19/00A61Q19/08
CPCA61K31/7028A61K31/192C12Q1/6883A61K36/48C12Q1/6876A61K31/4365C12Q2600/106A61K31/155A61K38/16A61K31/41C12Q2600/158A61K31/381A61K31/4196A61K35/32A61P17/00C12Q2600/148A61K8/60C12N15/11
Inventor F·贝尔内C·杜瓦尔O·德拉沙里埃S·努沃X·马拉
Owner LOREAL SA
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