2019
DOI: 10.1111/bjd.18033
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Pathophysiology of pachyonychia congenita‐associated palmoplantar keratoderma: new insights into skin epithelial homeostasis and avenues for treatment

Abstract: Summary Background Pachyonychia congenita (PC), a rare genodermatosis, primarily affects ectoderm‐derived epithelial appendages and typically includes oral leukokeratosis, nail dystrophy and very painful palmoplantar keratoderma (PPK). PC dramatically impacts quality of life although it does not affect lifespan. PC can arise from mutations in any of the wound‐repair‐associated keratin genes KRT6A, KRT6B, KRT6C, KRT16 or KRT17. There is no cure for this condition, and current treatment options for PC symptoms a… Show more

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Cited by 46 publications
(40 citation statements)
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References 114 publications
(226 reference statements)
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“…The K6/K16 keratin pairing, which is robustly wound-inducible, supports and promotes a number of cellular functions including structural integrity [17,24,39], cell migration [8,40], keratinocyte differentiation [41], regulation of innate immunity [7] and redox homeostasis [12,42]. Disruption of many of these cellular functions is poised to play a role in the pathophysiology of PC, in particular, in oral and palmoplantar keratoderma lesions [43]. Mitochondria represent the main cellular protagonist for regulation of ROS, which it achieves mainly via preserving the integrity and promoting the efficiency of the electron transport chain.…”
Section: Discussionmentioning
confidence: 99%
“…The K6/K16 keratin pairing, which is robustly wound-inducible, supports and promotes a number of cellular functions including structural integrity [17,24,39], cell migration [8,40], keratinocyte differentiation [41], regulation of innate immunity [7] and redox homeostasis [12,42]. Disruption of many of these cellular functions is poised to play a role in the pathophysiology of PC, in particular, in oral and palmoplantar keratoderma lesions [43]. Mitochondria represent the main cellular protagonist for regulation of ROS, which it achieves mainly via preserving the integrity and promoting the efficiency of the electron transport chain.…”
Section: Discussionmentioning
confidence: 99%
“…In the following stages, the Nrf2‐linked inflammatory cascade becomes involved. The latter, in particular, presents potential targets for intervention, given the availability of modulators of Nrf2 activity …”
mentioning
confidence: 99%
“…A Krt16 null mouse model with a palmoplantar keratoderma (PPK) similar to that found in patients with PC has been developed to improve the study of the disease mechanisms underlying PC. In the mouse model, there is a dramatic loss of keratin 9 in the footpad skin keratinocytes . Krt9 null mice also develop calluses, indicating that keratin 9 is likely to be important in the development of PPK .…”
mentioning
confidence: 99%