TY - JOUR
T1 - Paired Transcriptomic and Proteomic Analysis Implicates IL-1β in the Pathogenesis of Papulopustular Rosacea Explants
AU - Harden, Jamie L.
AU - Shih, Yi Hsien
AU - Xu, Jin
AU - Li, Rui
AU - Rajendran, Divya
AU - Hofland, Hans
AU - Chang, Anne Lynn S.
N1 - Funding Information:
This study was funded by Dermira. YHS is partially funded by a research award from Taipei Medical University (Taipei, Taiwan). This study was approved by Stanford University’s Human Subject’s Panel, protocol number 41443. Part of the data from this study has been presented as a late-breaking poster at the 77th Annual Meeting of the Society for Investigative Dermatology, Chicago, USA, 8–11 May 2019.
Funding Information:
This study was funded by Dermira. YHS is partially funded by a research award from Taipei Medical University (Taipei, Taiwan). This study was approved by Stanford University's Human Subject's Panel, protocol number 41443. Part of the data from this study has been presented as a late-breaking poster at the 77th Annual Meeting of the Society for Investigative Dermatology, Chicago, USA, 8?11 May 2019. Conceptualization: JLH; Data Curation: JLH, YHS, JX, RL; Formal Analysis: JLH, YHS, JX, RL; Funding Acquisition: HH; Investigation: JLH, YHS, DR; Methodology: JLH; Project Administration: JLH, YHS, DR, HH, ALSC; Resources: JLH, YHS, JX, RL, DR, HH, ALSC; Software: JX, RL; Supervision: HH, ALSC; Validation: JLH, YHS; Visualization: JLH, YHS, ALSC; Writing - Original Draft Preparation: JLH, YHS; Writing - Review and Editing: JLH, YHS, DR, HH, ALSC
Publisher Copyright:
© 2021 The Authors
PY - 2021/4
Y1 - 2021/4
N2 - Papulopustular rosacea (PPR) is a chronic inflammatory skin disease with limited treatment options. Although multiple pathways have been described to be upregulated in PPR, a mechanistic understanding of the key drivers and interaction between pathways in PPR pathology is lacking. In this study, we utilized PPR skin biopsy explants to integrate both differentially expressed genes and differentially expressed proteins in paired nonlesional and lesional PPR tissue (n = 5 patients). The results of this study identified 92 differentially expressed genes and 20 differentially expressed proteins between paired PPR lesional and nonlesional explants. MAPK and TNF signaling pathways were the most significantly upregulated pathways in PPR lesional tissue and aligned with differently expressed proteins identified in this study. Both MAPK and TNF signaling pathways highlighted IL-1β as a potential central mediator for PPR pathogenesis. In support of this, stimulation of nonlesional explants with IL-1β resulted in transcriptomic and proteomic profiles similar to those of lesional PPR. In this integrative transcriptomic and quantitative protein analysis, we identified several inflammatory genes, proteins, and pathways, which may be contributing to PPR, as well as highlighted a potential role of IL-1β in driving inflammation in PPR.
AB - Papulopustular rosacea (PPR) is a chronic inflammatory skin disease with limited treatment options. Although multiple pathways have been described to be upregulated in PPR, a mechanistic understanding of the key drivers and interaction between pathways in PPR pathology is lacking. In this study, we utilized PPR skin biopsy explants to integrate both differentially expressed genes and differentially expressed proteins in paired nonlesional and lesional PPR tissue (n = 5 patients). The results of this study identified 92 differentially expressed genes and 20 differentially expressed proteins between paired PPR lesional and nonlesional explants. MAPK and TNF signaling pathways were the most significantly upregulated pathways in PPR lesional tissue and aligned with differently expressed proteins identified in this study. Both MAPK and TNF signaling pathways highlighted IL-1β as a potential central mediator for PPR pathogenesis. In support of this, stimulation of nonlesional explants with IL-1β resulted in transcriptomic and proteomic profiles similar to those of lesional PPR. In this integrative transcriptomic and quantitative protein analysis, we identified several inflammatory genes, proteins, and pathways, which may be contributing to PPR, as well as highlighted a potential role of IL-1β in driving inflammation in PPR.
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U2 - 10.1016/j.jid.2020.08.013
DO - 10.1016/j.jid.2020.08.013
M3 - Article
C2 - 32941918
AN - SCOPUS:85092760772
SN - 0022-202X
VL - 141
SP - 800
EP - 809
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -