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Kallikrein-related peptidase 7 (KLK7) is a chymotrypsin-like serine peptidase that plays a crucial role in regulating skin desquamation. KLK7 expression is highly upregulated in atopic dermatitis (AD) skin lesions in both humans and mice. Th2-lymphocyte-derived cytokines, including interleukin (IL)-4 and IL-13, have been shown to promote KLK7 expression in keratinocytes in patients with AD. However, the molecular mechanism underlying KLK7 expression remains poorly understood. Here, we demonstrated that the EGR-1-binding sequence (EBS) in the promoter region of KLK7 played a crucial role in IL-13-induced KLK7 transcription. Disruption of the EBS induced by a point mutation inhibited IL-13-induced KLK7 promoter activity. EGR-1 was shown to directly bind to the EBS, and EGR1 knockdown with shRNA abrogated IL-13-induced KLK7 expression. Using Egr1 knockout mice, we showed that Egr-1 was necessary for KLK7 expression in AD-like lesions induced by the repeated topical application of 2,4-dinitrobenzene on the dorsal skin of mice. We also demonstrated that the ERK1/2 mitogen-activated protein kinase (MAPK) pathway was responsible for EGR-1-dependent KLK7 transcription in response to IL-13 stimulation. Our findings delineate a signaling pathway that contributes to the regulation of KLK7 expression through the IL13-ERK MAPK-EGR1 signaling axis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

(E)-1-(2-hydroxyphenyl)-3-(2-methoxynaphthalen-1-yl)prop-2-en-1-one (HMP) is a novel synthetic naphthal chalcone derivative. The aim of this study was to investigate the mode of action underlying the antitumor activity of HMP. We found that treatment with HMP potently inhibited the clonogenicity and triggered cell death in HCT116 colon cancer cells. Flow cytometry showed that HMP induced an increase in the population of sub-G 0 /G 1 -phase cells. Annexin V binding assay revealed that HMP triggered apoptotic cell death. Furthermore, HMP stimulated the cleavages of caspase-7 and its substrate poly (ADP-ribose) polymerase (PARP). HMP promoted γ-H2AX formation and the production of reactive oxygen species (ROS), and up-regulated expression of the tumor suppressor p53. Interestingly, HMP-induced caspase-7 processing was not completely abrogated in p53-null (p53 -/- ) HCT116 cells, suggesting that p53-dependent and -independent mechanisms are involved in HMP-induced apoptosis. Egr-1, a zinc finger transcription factor, was upregulated by HMP. Silencing of Egr-1 by shRNA significantly reduced HMP-induced caspase-7 and PARP cleavages, regardless of p53 status. These results suggest that HMP triggers caspase-mediated apoptosis through two distinct mechanisms involving p53-dependent and p53-independent, Egr-1-dependent pathways., (Copyright © 2016 Elsevier Inc. All rights reserved.)