Nrf2-Mediated Fibroblast Reprogramming Drives Cellular Senescence by Targeting the Matrisome

• Published in: Developmental cell Vol. 46; no. 2; pp. 145 - 161.e10
• Main Authors: Hiebert, Paul, Wietecha, Mateusz S., Cangkrama, Michael, Haertel, Eric, Mavrogonatou, Eleni, Stumpe, Michael, Steenbock, Heiko, Grossi, Serena, Beer, Hans-Dietmar, Angel, Peter, Brinckmann, Jürgen, Kletsas, Dimitris, Dengjel, Jörn, Werner, Sabine
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.07.2018
• Subjects: Animals; Antioxidants - metabolism; cancer; cancer-associated fibroblast; Carcinogenesis - metabolism; Cell Proliferation; Cellular Reprogramming - physiology; Cellular Senescence - physiology; extracellular matrix; Extracellular Matrix - physiology; fibroblast; Fibroblasts - physiology; Gene Expression Regulation - physiology; Mice; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; NF-E2-Related Factor 2 - physiology; Nrf2; Oxidative Stress - physiology; SASP; senescence; Skin - metabolism; wound healing; Wound Healing - physiology; cancer-associated fibroblast; senescence; wound healing; fibroblast; Nrf2; cancer; SASP; extracellular matrix

Nrf2 is a key regulator of the antioxidant defense system, and pharmacological Nrf2 activation is a promising strategy for cancer prevention and promotion of tissue repair. Here we show, however, that activation of Nrf2 in fibroblasts induces cellular senescence. Using a combination of transcriptomi...