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Feasibility study for clinical application of caspase-3 inhibitors in Pemphigus vulgaris

(2017) EXPERIMENTAL DERMATOLOGY. 26(12). p.1274-1277
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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 (casp3(EKO)) 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.
Keywords
MICE, Clinical application, Desmoglein 3, non-apoptotic caspase-3, Pemphigus, vulgaris signaling

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MLA
Hariton, William VJ, Arnaud Galichet, Tom Vanden Berghe, et al. “Feasibility Study for Clinical Application of Caspase-3 Inhibitors in Pemphigus Vulgaris.” EXPERIMENTAL DERMATOLOGY 26.12 (2017): 1274–1277. Print.
APA
Hariton, W. V., Galichet, A., Vanden Berghe, T., Overmiller, A. M., Mahoney, M. G., Declercq, W., & Müller, E. J. (2017). Feasibility study for clinical application of caspase-3 inhibitors in Pemphigus vulgaris. EXPERIMENTAL DERMATOLOGY, 26(12), 1274–1277.
Chicago author-date
Hariton, William VJ, Arnaud Galichet, Tom Vanden Berghe, Andrew M Overmiller, My G Mahoney, Wim Declercq, and Eliane J Müller. 2017. “Feasibility Study for Clinical Application of Caspase-3 Inhibitors in Pemphigus Vulgaris.” Experimental Dermatology 26 (12): 1274–1277.
Chicago author-date (all authors)
Hariton, William VJ, Arnaud Galichet, Tom Vanden Berghe, Andrew M Overmiller, My G Mahoney, Wim Declercq, and Eliane J Müller. 2017. “Feasibility Study for Clinical Application of Caspase-3 Inhibitors in Pemphigus Vulgaris.” Experimental Dermatology 26 (12): 1274–1277.
Vancouver
1.
Hariton WV, Galichet A, Vanden Berghe T, Overmiller AM, Mahoney MG, Declercq W, et al. Feasibility study for clinical application of caspase-3 inhibitors in Pemphigus vulgaris. EXPERIMENTAL DERMATOLOGY. 2017;26(12):1274–7.
IEEE
[1]
W. V. Hariton et al., “Feasibility study for clinical application of caspase-3 inhibitors in Pemphigus vulgaris,” EXPERIMENTAL DERMATOLOGY, vol. 26, no. 12, pp. 1274–1277, 2017.
@article{8546097,
  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 (casp3(EKO)) 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.},
  author       = {Hariton, William VJ and Galichet, Arnaud and Vanden Berghe, Tom and Overmiller, Andrew M and Mahoney, My G and Declercq, Wim and Müller, Eliane J},
  issn         = {0906-6705},
  journal      = {EXPERIMENTAL DERMATOLOGY},
  keywords     = {MICE,Clinical application,Desmoglein 3,non-apoptotic caspase-3,Pemphigus,vulgaris signaling},
  language     = {eng},
  number       = {12},
  pages        = {1274--1277},
  title        = {Feasibility study for clinical application of caspase-3 inhibitors in Pemphigus vulgaris},
  url          = {http://dx.doi.org/10.1111/exd.13458},
  volume       = {26},
  year         = {2017},
}

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