EGR-1 acts as a transcriptional activator of KLK7 under IL-13 stimulation.

Hyunjin Yeo, Sung Shin Ahn, Jeong Yeon Lee, Soon Young Shin

Biochemical and biophysical research communications 2021 Jan 01

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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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Hyunjin Yeo, Sung Shin Ahn, Jeong Yeon Lee, Soon Young Shin. EGR-1 acts as a transcriptional activator of KLK7 under IL-13 stimulation. Biochemical and biophysical research communications. 2021 Jan 01;534:303-309