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| Status |
Public on Oct 01, 2020 |
| Title |
Profibrotic regulation of FGFR3 signaling in fibroblasts |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
We employed dermal fibroblasts isolated from Fgfr3G374Rneo+ mice, which do not express functional Fgfr3 (Fgfr3KO), from Fgfr3G374Rneo- mice with ligand-independent constitutive activation of Fgfr3 (Fgfr3Act) and from wildtype (WT) mice with normal expression of Fgfr3. Total RNA from these murine dermal fibroblasts (passage 4) were extracted and after quality control, were hybridized to the murine genome U74 gene chip. We have identified that Fgfr3 regulates important profibrotic pathways in fibroblasts. Selective upregulation of fibroblast growth factor receptor 3 (FGFR3) and its ligand FGF9 promote fibroblast activation and tissue fibrosis Transcriptome profiling, in silico analysis and functional experiments revealed that FGFR3 synergistically induces multiple profibrotic pathways including Endothelin-, Interleukin-4- and CTGF-signaling in a CREB-dependent manner. Inhibition of FGFR3 signaling by fibroblast-specific knockout of FGFR3 or FGF9 or pharmacological inhibition of FGFR3 inhibited fibroblast activation and attenuated experimental skin fibrosis. We have characterized FGFR3 as an upstream regulator of a network of profibrotic mediators and as a potential target for the treatment of fibrosis.
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| Overall design |
We used microarrays to detail the global program of gene expression in fibroblasts.
Three conditions, constitutive activation of Fgfr3 and Fgfr3 knockout with wildtype control (n=3 for all groups).
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| Contributor(s) |
Chakraborty D, Zhu H, Distler J |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Apr 14, 2020 |
| Last update date |
Oct 03, 2020 |
| Contact name |
Debomita Chakraborty |
| E-mail(s) |
Debomita.Chakraborty@uk-erlangen.de
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| Organization name |
Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen
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| Street address |
Ulmenweg 18
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| City |
Erlangen |
| ZIP/Postal code |
91054 |
| Country |
Germany |
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| Platforms (1) |
| GPL81 |
[MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA625273 |
