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Publication : KLF4 is a therapeutically tractable brake on fibroblast activation that promotes resolution of pulmonary fibrosis.

First Author  Penke LR Year  2022
Journal  JCI Insight Volume  7
Issue  16 PubMed ID  35852857
Mgi Jnum  J:330838 Mgi Id  MGI:7340737
Doi  10.1172/jci.insight.160688 Citation  Penke LR, et al. (2022) KLF4 is a therapeutically tractable brake on fibroblast activation that promotes resolution of pulmonary fibrosis. JCI Insight 7(16):e160688
abstractText  There is a paucity of information about potential molecular brakes on the activation of fibroblasts that drive tissue fibrosis. The transcription factor Kruppel-like factor 4 (KLF4) is best known as a determinant of cell stemness and a tumor suppressor. We found that its expression was diminished in fibroblasts from fibrotic lung. Gain- and loss-of-function studies showed that KLF4 inhibited fibroblast proliferation, collagen synthesis, and differentiation to myofibroblasts, while restoring their sensitivity to apoptosis. Conditional deletion of KLF4 from fibroblasts potentiated the peak degree of pulmonary fibrosis and abrogated the subsequent spontaneous resolution in a model of transient fibrosis. A small molecule inducer of KLF4 was able to restore its expression in fibrotic fibroblasts and elicit resolution in an experimental model characterized by more clinically relevant persistent pulmonary fibrosis. These data identify KLF4 as a pivotal brake on fibroblast activation whose induction represents a therapeutic approach in fibrosis of the lung and perhaps other organs.
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