Abstract:
:The potentially severe side effects of systemic corticosteroids and immunosuppressants used in Pemphigus vulgaris (PV) call for novel therapeutic approaches. In this context, pharmacological inhibition of major pathogenic signalling effectors represents a promising alternative. However, we have also shown that overinhibition of effectors required for epidermal homeostasis can exacerbate PV pathophysiology implicating transepidermal keratinocyte fragility. A feedforward target validation therefore preferentially includes studies on knockout mouse models. We previously reported on successful amelioration of PV blisters following inhibition of non-apoptotic, low-level caspase-3. Here, we use conditional, keratinocyte-specific caspase-3-deficient mice (casp3EKO ) to demonstrate (i) absence of keratinocyte fragility upon injection of the potent Dsg3-specific antibody AK23 and (ii) amelioration of blistering on the background of known signalling effectors. Our results provide the experimental proof of concept justifying translation of the caspase-3 inhibitor approach into PV clinical trials.
journal_name
Exp Dermatoljournal_title
Experimental dermatologyauthors
Hariton WVJ,Galichet A,Vanden Berghe T,Overmiller AM,Mahoney MG,Declercq W,Müller EJdoi
10.1111/exd.13458subject
Has Abstractpub_date
2017-12-01 00:00:00pages
1274-1277issue
12eissn
0906-6705issn
1600-0625journal_volume
26pub_type
信件abstract::For many years, the function of the sebaceous gland (SG) was underestimated and suggested by Albert M. Kligman as a remnant of human development, a 'living fossil with a past but no future'. However, the last two decades of studies and the discovery of neuro-endocrine pathways in skin have determined the importance of...
journal_title:Experimental dermatology
pub_type: 评论,杂志文章
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abstract::Dendritic cells (DC) are key elements of the immune system. In peripheral tissues, they function as sentinels taking up and processing antigens. After migration to the draining lymph nodes, the DC either present antigenic peptides by themselves or transfer them to lymph node-resident DC. The skin is the primary interf...
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journal_title:Experimental dermatology
pub_type: 杂志文章,评审
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journal_title:Experimental dermatology
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abstract::Dermal papilla cells (DPC) control the growth character of the hair follicle through their elaboration of mitogenic factors and extracellular matrix components. Further, the dermal papilla is a primary site of androgen action in the hair follicle. Interleukin-1alpha (IL-1alpha) is prominent in skin wounding and inflam...
journal_title:Experimental dermatology
pub_type: 杂志文章
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abstract::Keloid is a dermal proliferative disorder characterized by the excessive proliferation and migration of keratinocytes and fibroblasts. Over-activation of the serine/threonine protein kinase, mammalian target of rapamycin (mTOR), plays a pivotal role in the process. Here, we show that both mTOR complex 1 (mTORC1) and m...
journal_title:Experimental dermatology
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journal_title:Experimental dermatology
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abstract::Human sebaceous gland possesses all the steroidogenic enzymes required for androgen synthesis. It remains unclear whether the testosterone produced in situ mainly derives from circulating dehydroepiandrosterone (DHEA) or from de novo synthesis utilizing serum cholesterol. Using testosterone radioimmunoassay, we found ...
journal_title:Experimental dermatology
pub_type: 信件
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journal_title:Experimental dermatology
pub_type: 杂志文章
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journal_title:Experimental dermatology
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journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.0906-6705.2004.00220.x
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journal_title:Experimental dermatology
pub_type: 信件
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abstract::Chimeric antigen receptor (CAR)-T cells are one of the impressive recent success stories of anti-cancer immunotherapy. Especially in haematological malignancies, this treatment strategy has shown promising results leading to the recent approval of two CAR-T cell constructs targeting CD19 in the United States and the E...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.13792
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abstract::Psoriasis is a chronic immune-mediated skin disease in which the balance in the interplay of immune cells and keratinocytes is disturbed. MicroRNAs (miRNAs) are endogenous small regulatory RNAs that stabilize cellular phenotypes and fine-tune signal transduction feedback loops through the regulation of gene networks. ...
journal_title:Experimental dermatology
pub_type: 杂志文章,评审
doi:10.1111/exd.12469
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journal_title:Experimental dermatology
pub_type: 信件
doi:10.1111/exd.12613
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abstract::Microsatellite instability and reduced expression of mismatch repair proteins were reported in melanomas. However, little is known about mutational changes of the mismatch repair genes in radial growth-phase melanoma especially following UVB irradiation. To investigate these changes, an in vitro system consisting of r...
journal_title:Experimental dermatology
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journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1034/j.1600-0625.2001.010003155.x
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abstract::Nilotinib (AMN), a second-generation tyrosine kinase inhibitor, induces apoptosis in various cancer cells, and our recent study showed that AMN effectively reduced the viability of human ovarian cancer cells via mitochondrion-dependent apoptosis. The effect of AMN in the melanogenesis of melanoma cells is still unclea...
journal_title:Experimental dermatology
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abstract::Electrical stimulation is being used in variable skin therapeutic conditions. There have been clinical studies demonstrating the positive effect of electrical stimuli on hair regrowth. However, the underlying exact mechanism and optimal parameter settings are not clarified yet. To investigate the effects of different ...
journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/exd.12827
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journal_title:Experimental dermatology
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journal_title:Experimental dermatology
pub_type: 杂志文章
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journal_title:Experimental dermatology
pub_type: 杂志文章
doi:10.1111/j.1600-0625.1994.tb00287.x
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journal_title:Experimental dermatology
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pub_type: 杂志文章
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journal_title:Experimental dermatology
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pub_type: 临床试验,杂志文章
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journal_title:Experimental dermatology
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journal_title:Experimental dermatology
pub_type: 杂志文章
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