Figure 1.

The role of p38 MAPK in the induction of pemphigus vulgaris (PV). There are at least three potential p38-MAPK-related mechanisms involved in the pathogenesis and/or the progression of PV. (a) The binding of pathogenic autoantibodies targeting Dsg3 in keratinocytes initiates an array of signals leading to the activation of p38 MAPK cascade with subsequent phosphorylation of MAPKAPK (mitogen-activated protein kinase-activated protein kinases 2/3) and heat shock protein 27 (Hsp 27). The final outcome of these events is actin filaments reorganization and induction of acantholysis [19]; (b) p38 MAPK, MAPKAPK, and Hsp27 may form a complex (signalosome) that regulates the reorganization of actin filaments and the induction of acantholysis [20]; (c) studies in p38−/− keratinocytes demonstrate a p38 MAPK-independent blister formation. The subsequent activation of this pathway, however, can lead to de novo depletion of multiple desmosomal molecules, further facilitating spontaneous blister formation [21]. This latter hypothesis indicates that p38 MAPK signaling may not be responsible for the induction of PV but could play a role for the progression of the disease.