Caveolin-1 as a pathophysiological factor and target in psoriasis

Kruglikov, Ilja L.; Scherer, Philipp E.

doi:10.1038/s41514-019-0034-x

Cited by 28 publications

(36 citation statements)

References 106 publications

(127 reference statements)

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“…Dysregulation of Cav1 expression in the human skin is associated with hyperproliferative diseases such as melanoma and non-melanoma cancers but also psoriasis (Carè et al, 2011; Gheida et al, 2018; Kruglikov and Scherer, 2019). In melanoma, Cav1 function remains very controversial, since it is recognized as a tumor suppressor and an oncogene (Felicetti et al, 2009; Trimmer et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Caveolae coupling of melanocytes signaling and mechanics is required for human skin pigmentation

Domingues

Hurbain

Gilles-Marsens

et al. 2019

Preprint

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22Tissue homeostasis requires regulation of cell-cell communication, which relies on signaling 23 molecules and cell contacts. In skin epidermis, keratinocytes secrete specific factors transduced 24 by melanocytes into signaling cues to promote their pigmentation and dendrite outgrowth, while 25 melanocytes transfer melanin pigments to keratinocytes to convey skin photoprotection. How 26 epidermal cells integrate these functions remains poorly characterized. Here, we found that 27 caveolae polarize in melanocytes and are particularly abundant at melanocyte-keratinocyte 28 interface. Caveolae in melanocytes are sensitive to ultra-violet radiations and miRNAs released 29 by keratinocytes. Preventing caveolae formation in melanocytes results in increased production 30 of intracellular cAMP and melanin pigments, but decreases cell protrusions, cell-cell contacts, 31 pigment transfer and epidermis pigmentation. Altogether, our data establish that, in 32 melanocytes, caveolae serve as key molecular hubs that couple signaling outputs from 33 keratinocytes to mechanical plasticity. This process is crucial to maintain cell-cell contacts and 34 intercellular communication, skin pigmentation and tissue homeostasis. 84Epidermal melanocytes and keratinocytes are in constant communication, not only via secreted 85 factors and exosomes that modulate cellular responses, but also by the physical contacts they 86 establish to maintain the tissue homeostasis and pigmentation. Here, we report a new function 87 for caveolae, which, by integrating the biochemical and mechanical behavior of melanocytes, 88 control melanin transfer to keratinocytes and epidermis pigmentation. Altogether, this study 89 provides the first evidence for a physiologic role of caveolae as a molecular sensing platform 90 required for the homeostasis of the largest human tissue, the skin epidermis. 91 5 Results 92 Caveolae polarize in melanocytes and are positively-regulated by keratinocytes-secreted 93 factors 94Melanocytes and keratinocytes establish a complex intercellular dialogue required for skin 95 photoprotection. 2D-co-culture systems, where these two cell types share the same medium, 96have been widely used to study intercellular communication and pigment transfer between 97 epidermal cells (Hirobe, 2005; Lei et al., 2002). To evaluate the distribution of caveolae within 98 the epidermal unit in 2D, normal human melanocytes and keratinocytes were co-cultured and 99 labelled for the two constituents of caveolae, Cav1 or Cavin1. Immunofluorescence microscopy 100 revealed that both Cav1 and Cavin1, and therefore caveolae, were asymmetrically distributed in 101 melanocytes (Figures 1A and B), which were identified by the abundant staining of the 102 premelanosome protein PMEL [hereafter referred as melanin, see Experimental Procedures; 103 (Raposo et al., 2001)]. This polarization was not observed in keratinocytes.104 Cells can break their symmetry in response to local external chemical and/or mechanical cues 105 such as signaling molecules and/or cell-ce...

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Section: Discussionmentioning

confidence: 99%

Caveolae coupling of melanocytes signaling and mechanics is required for human skin pigmentation

Domingues

Hurbain

Gilles-Marsens

et al. 2019

Preprint

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“…Previous analysis demonstrated its essential role in the pathogenesis of skin diseases such as psoriasis and hypertrophic scarring. [3,4] Here, we propose that Cav-1 is also casually involved in pathogenesis of acne. Etiopathogenic factors in acne such as follicular hyperkeratinization, hyperseborrhea and pathogenic behaviour of C. acnes all demonstrate a clear dependence on Cav-1 expression.…”

Section: Con Clus Ionmentioning

confidence: 90%

“…[14] Cav-1 is involved in the internalization and intracellular degradation of TGF-β receptors, [15] providing an inverse correlation between TGF-β1 and Cav-1 in different hyperproliferative and inflammatory conditions. [3,4] Correspondingly, the observed overexpression of TGF-β1 points to a local deficiency of Cav-1 in acne lesions.…”

Section: Introductionmentioning

confidence: 89%

“…[1][2][3] Low levels of Cav-1 expression in tissues are generally connected with the appearance of hyperproliferative and inflammatory conditions and are also substantially involved in psoriasis and scarring. [3,4] Keratinocytes in which lipid rafts are disrupted are also associated with the appearance of atopic dermatitis. [5] Acne vulgaris is the most common chronic inflammatory skin disease related to pilosebaceous units (PSUs).…”

Section: Introductionmentioning

confidence: 99%

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Caveolin‐1 as a possible target in the treatment for acne

Kruglikov¹,

Scherer

2019

Experimental Dermatology

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Expression of caveolin-1 (Cav-1) is an important pathophysiological factor in acne.Cav-1 strongly interacts with such well-recognized etiopathogenic factors such as hyperseborrhea, follicular hyperkeratinization and pathogenicity of Cutibacterium acnes. Cav-1 is a strong negative regulator of transforming growth factor beta (TGFβ) expression. It acts as a critical determinant of autophagy, which is significantly induced in acne lesions through C. acnes and by absorption of fatty acids. Cav-1 also demonstrates different correlations with the development of innate immunity. We propose that normalization of Cav-1 expression can serve as a target in anti-acne therapy. K E Y W O R D Sacne, autophagy, C. acnes, caveolin, follicular hyperkeratinization, hyperseborrhea, innate immunity, pathophysiology

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“…In addition, direct physical interactions have been established between Cav-1 and some matrix metalloproteinases, heat shock proteins, toll-like and glucocorticoid receptors. Cav-1 is causally involved in processes such as collagen production, interaction of hyaluronan with plasma membranes, and the regulation of the autophagy [2][3][4][5]. Additionally, Cav-1 exists not only intracellularly, but it can be transported within the tissue, and even between adjacent tissues, via mechanisms involving exosomal exchange [6] providing a long-range distribution of this protein in the skin.…”

Section: Introductionmentioning

confidence: 99%

Caveolin as a Universal Target in Dermatology

Kruglikov¹,

Scherer

2019

IJMS

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Caveolin-1 is strongly expressed in different dermal and subdermal cells and physically interacts with signaling molecules and receptors, among them with transforming growth factor beta (TGF-β), matrix metalloproteinases, heat shock proteins, toll-like and glucocorticoid receptors. It should therefore be heavily involved in the regulation of cellular signaling in various hyperproliferative and inflammatory skin conditions. We provide an overview of the role of the caveolin-1 expression in different hyperproliferative and inflammatory skin diseases and discuss its possible active involvement in the therapeutic effects of different well-known drugs widely applied in dermatology. We also discuss the possible role of caveolin expression in development of the drug resistance in dermatology. Caveolin-1 is not only an important pathophysiological factor in different hyperproliferative and inflammatory dermatological conditions, but can also serve as a target for their treatment. Targeted regulation of caveolin is likely to serve as a new treatment strategy in dermatology.

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Caveolin-1 as a pathophysiological factor and target in psoriasis

Cited by 28 publications

References 106 publications

Caveolae coupling of melanocytes signaling and mechanics is required for human skin pigmentation

Caveolae coupling of melanocytes signaling and mechanics is required for human skin pigmentation

Caveolin‐1 as a possible target in the treatment for acne

Caveolin as a Universal Target in Dermatology

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