The importance of caveolins and caveolae to dermatology: Lessons from the caves and beyond

Egger, Andjela; Rajabi‐Estarabadi, Ali; Williams, Natalie M.; Resnik, Sydney R.; Fox, Joshua; Wong, Lulu L.; Jozic, Ivan

doi:10.1111/exd.14068

Cited by 19 publications

(14 citation statements)

References 204 publications

(363 reference statements)

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“…[ 49,50,65,67,69 ] The activation of the rapid response to vitamin D requires the interaction of membrane‐associated PDIA3 with caveolin 1 (CAV1) [ 76,78,79 ] (Figure 2,5), the main protein of small invaginations of the plasma membrane called of caveolae. [ 80 ] The interaction of vitamin D with membrane‐associated PDIA3 has important physiological implications. For example, PDIA3 but not VDR is essential for the activation of protein kinase C (PKC) signalling pathway [ 81 ] or the protection of cells against UV‐induced DNA damage, in particular thymine dimer formation.…”

Section: Evidence For Membrane Signalling Of Vitamin Dmentioning

confidence: 99%

Vitamin D receptor(s): In the nucleus but also at membranes?

Żmijewski

Carlberg

2020

Experimental Dermatology

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Secosteroids are steroid compounds with an open Bring commonly found in fungi (vitamin D 2), plants, invertebrates and vertebrates (vitamin D 3). Evolutionary, vitamin D 3 is a very old molecule, [1] which is created in a non-enzymatic reaction when the direct cholesterol precursor 7-dehydrocholesterol is exposed to UV-B (290-320 nm), [2,3] that is, cholesterol synthesizing species use(d) vitamin D 3 for UV-B scavenging [4] (Figure 1). This implies that also humans can synthesize vitamin D 3 in their skin. Through the action of a variety of cytochrome P450 (CYP) enzymes numerous vitamin D metabolites are created, [5] of which 25-hydroxyvitamin D 3 (25(OH)D 3) is the most stable (serum half-life some 3 weeks [6]) and abundant (a vitamin D sufficient person should have 25(OH)D 3 serum concentration of at least 75 nM [7]). The starting point of what is called today vitamin D endocrinology was some 550 million years ago, when in a boneless fish a receptor evolved that bound with high affinity the metabolite 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3). [8] This high affinity

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Section: Evidence For Membrane Signalling Of Vitamin Dmentioning

confidence: 99%

Vitamin D receptor(s): In the nucleus but also at membranes?

Żmijewski

Carlberg

2020

Experimental Dermatology

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“…In this context, the plasma membrane of eHFSCs, namely its caveolae and their principal structural component, caveolin-1 (Cav1) [ 49 , 50 ], has not yet been considered. Cav1 compartmentalizes various signal transduction molecules and thus orchestrates numerous transmembrane signaling events involved in epithelial cell function including (but not limited to) endocytosis, lipid transport, signal transduction, inflammation, as well as cellular migration and proliferation ( Figure 1 b) (reviewed in [ 3 ]).…”

Section: Introductionmentioning

confidence: 99%

A Cell Membrane-Level Approach to Cicatricial Alopecia Management: Is Caveolin-1 a Viable Therapeutic Target in Frontal Fibrosing Alopecia?

et al. 2021

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Irreversible destruction of the hair follicle (HF) in primary cicatricial alopecia and its most common variant, frontal fibrosing alopecia (FFA), results from apoptosis and pathological epithelial-mesenchymal transition (EMT) of epithelial HF stem cells (eHFSCs), in conjunction with the collapse of bulge immune privilege (IP) and interferon-gamma-mediated chronic inflammation. The scaffolding protein caveolin-1 (Cav1) is a key component of specialized cell membrane microdomains (caveolae) that regulates multiple signaling events, and even though Cav1 is most prominently expressed in the bulge area of human scalp HFs, it has not been investigated in any cicatricial alopecia context. Interestingly, in mice, Cav1 is involved in the regulation of (1) key HF IP guardians (TGF-β and α-MSH signaling), (2) IP collapse inducers/markers (IFNγ, substance P and MICA), and (3) EMT. Therefore, we hypothesize that Cav1 may be an unrecognized, important player in the pathobiology of cicatricial alopecias, and particularly, in FFA, which is currently considered as the most common type of primary lymphocytic scarring alopecia in the world. We envision that localized therapeutic inhibition of Cav1 in management of FFA (by cholesterol depleting agents, i.e., cyclodextrins/statins), could inhibit and potentially reverse bulge IP collapse and pathological EMT. Moreover, manipulation of HF Cav1 expression/localization would not only be relevant for management of cicatricial alopecia, but FFA could also serve as a model disease for elucidating the role of Cav1 in other stem cell- and/or IP collapse-related pathologies.

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“…Decorin and caveolin1 are inhibitors of the TGF-β1 signaling pathway [63][64][65]. Moreover, caveolin1 negatively regulates β-catenin during wound healing [66]. Regardless, Angio PRP wounds and WT skin exhibit similar decreased TGFβ1 and β-catenin levels (Fig.…”

Section: Discussionmentioning

confidence: 89%

Platelets and Pro-Angiogenic Circulating Cells Accelerate Skin Wound Healing

Erratico¹,

Belicchi

Meregalli

et al. 2021

Preprint

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BackgroundDelayed wound healing and chronic skin lesions represent a major health problem. Over the past years, growth factors mediated by platelet-rich plasma (PRP) and cell-based therapies were developed as effective and affordable treatment able to improve wound healing capacity. However, the precise molecular mechanism through which PRP exhibits its beneficial effects remains unrevealed. Herein we show that a combination of PRP and pro-angiogenic cells (AngioPRP) could exert a synergistic positive effect on keratinocyte proliferation and angiogenesis accelerating wound healing.MethodWe designed a sterile and closed class IIa device (NovySep) for single use only to collect blood-derived mononucleated cells and the plasma phase after centrifugation without opening the system. We performed in vitro and in vivo wound healing experiments to assess the angiogenic potential of AngioPRP; we evaluated the extracellular matrix remodeling and the physical properties of treated wounds through mechanical (stress-strain test) and proteomics analysis.ResultAngioPRP enhanced wound healing by promoting uniform regeneration of the basal and granular layers and vessel remodeling. We coupled this effect with normalization of mechanical properties of rescued mouse wounds, which is sustained by a correct arrangement of elastin and collagen fibers. The network analysis-based protein–protein interactions of AngioPRP-treated wounds demonstrated a fingerprint of AngioPRP-related proteins that may provide the signal for a faster wound healing response which include Caveolin and EGFR/TGFβ/β-catenin pathways.ConclusionA combined treatment composed of PRP and a pool of pro-angiogenic/keratogenic cells (AngioPRP) may provide a more integrated method to supports wound healing, by promoting a cascade of events leading to the reduction of TGFβ1/β-catenin up-downstream signaling pathways. The molecular mechanism undergoing the support of AngioPRP to wound healing opens new perspectives in the treatment of skin injuries.

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The importance of caveolins and caveolae to dermatology: Lessons from the caves and beyond

Cited by 19 publications

References 204 publications

Vitamin D receptor(s): In the nucleus but also at membranes?

Vitamin D receptor(s): In the nucleus but also at membranes?

A Cell Membrane-Level Approach to Cicatricial Alopecia Management: Is Caveolin-1 a Viable Therapeutic Target in Frontal Fibrosing Alopecia?

Platelets and Pro-Angiogenic Circulating Cells Accelerate Skin Wound Healing

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