ArticlePloS one2013
Role for Krüppel-like transcription factor 11 in mesenchymal cell function and fibrosis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
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- Article
- KLF11 deficiency enhances chemokine generation and fibrosis in murine unilateral ureteral obstruction.PloS one · 2022Article
- Inactivation of the Euchromatic Histone-LysineFrontiers in cell and developmental biology · 2021Article
- Clinical and Functional Characteristics of a NovelJournal of diabetes research · 2021Article
- The Distinct Roles of Transcriptional Factor KLF11 in Normal Cell Growth Regulation and Cancer as a Mediator of TGF-β Signaling Pathway.International journal of molecular sciences · 2020Review
- Combined Targeting of G9a and Checkpoint Kinase 1 Synergistically Inhibits Pancreatic Cancer Cell Growth by Replication Fork Collapse.Molecular cancer research : MCR · 2020Article
- Combined AURKA and H3K9 Methyltransferase Targeting Inhibits Cell Growth By Inducing Mitotic Catastrophe.Molecular cancer research : MCR · 2017Article
- SP and KLF Transcription Factors in Digestive Physiology and Diseases.Gastroenterology · 2017Review
- Krüppel-like factors in mammalian stem cells and development.Development (Cambridge, England) · 2017Review
- KLF10 Mediated Epigenetic Dysregulation of Epithelial CD40/CD154 Promotes Endometriosis.Biology of reproduction · 2016Article
- Krüppel-like factor KLF10 deficiency predisposes to colitis through colonic macrophage dysregulation.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- The Aurora A-HP1γ pathway regulates gene expression and mitosis in cells from the sperm lineage.BMC developmental biology · 2015Article
- Membrane-to-Nucleus Signals and Epigenetic Mechanisms for Myofibroblastic Activation and Desmoplastic Stroma: Potential Therapeutic Targets for Liver Metastasis?Molecular cancer research : MCR · 2015Review
- A novel role for KLF14 in T regulatory cell differentiation.Cellular and molecular gastroenterology and hepatology · 2015Article
- Krüppel-like factor KLF10 regulates transforming growth factor receptor II expression and TGF-β signaling in CD8+ T lymphocytes.American journal of physiology. Cell physiology · 2015Article
- Ovarian steroids, stem cells and uterine leiomyoma: therapeutic implications.Human reproduction updateReview
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Krüppel-like factor 11 (KLF11) and the highly homologous KLF10 proteins are transcription factors originating from duplication of the Drosophila melanogaster ancestor cabut. The function of these proteins in epithelial cells has been previously characterized. In the current study, we report a functional role for KLF11 in mesenchymal cells and in mesenchymal cell dysfunction, namely, fibrosis, and subsequently perform a detailed cellular, molecular, and in vivo characterization of this phenomenon. We find that, in cultured mesenchymal cells, enhanced expression of KLF11 results in activated extracellular matrix pathways, including collagen gene silencing and matrix metalloproteinases activation without changes in tissue inhibitors of metalloproteinases. Combined, reporter and chromatin immunoprecipitation assays demonstrate that KLF11 interacts directly with the collagen 1a2 (COL1A2) promoter in mesenchymal cells to repress its activity. Mechanistically, KLF11 regulates collagen gene expression through the heterochromatin protein 1 gene-silencing pathway as mutants defective for coupling to this epigenetic modifier lose the ability to repress COL1A2. Expression studies reveal decreased levels of KLF11 during liver fibrogenesis after chemically induced injury in vivo. Congruently, KLF11(-/-) mice, which should be deficient in the hypothesized anti-fibrogenic brake imposed by this transcription factor, display an enhanced response to liver injury with increased collagen fibril deposition. Thus, KLFs expands the repertoire of transcription factors involved in the regulation of extracellular matrix proteins in mesenchymal cells and define a novel pathway that modulates the fibrogenic response during liver injury.
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