Activation of Nrf2 in fibroblasts promotes a skin aging phenotype via an Nrf2-miRNA-collagen axis
A "Matrix Biology" paper by the Werner group (IMHS) shows that activation of the Nrf2 transcription factor in fibroblasts causes reduced skin strength as seen during aging. This results from miRNA-mediated reduction of major collagens. The data identify Nrf2 as a promoter of age-related molecular and biomechanical skin features.
Aging is associated with progressive skin fragility and a tendency to tear, which can lead to severe clinical complications. Surprisingly, the underlying causes are poorly defined.
Using a combination of molecular and cellular biology, histology, imaging and biomechanical studies, Hiebert et al. show that constitutive genetic activation of the cytoprotective Nrf2 transcription factor in fibroblasts of mice suppresses collagen and elastin expression, resulting in reduced skin strength as seen in aged mice. The "aging matrisome" results in part from direct Nrf2-mediated overexpression of a network of microRNAs that target mRNAs of major skin collagens and other matrix components. The detection of high NRF2 activity in skin fibroblasts of aged individuals in vivo highlights the translational relevance of the mouse data. Together, these results identify activated NRF2 as a promoter of age-related molecular and biomechanical skin features.
Link to the publication in external page "Matrix Biology".