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| Status |
Public on May 02, 2023 |
| Title |
Repurposing DPP4-Inhibition to Improve Hair Follicle Activation and Regeneration |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Skin-injury and several diseases elicit fibrosis and induce hair follicle (HF)-growth arrest and loss. Resulting alopecia and disfiguration represent a severe burden for patients both physically and psychologically. Reduction of pro-fibrotic factors such as DPP4 might be a strategy to tackle this issue. We demonstrate DPP4-overrepresentation in settings with HF-growth arrest (telogen), HF-loss and non-regenerative wound areas in mice skin and human scalp. Topical DPP4-inhibition (DPP4i) with FDA/EMA-approved Sitagliptin (Sit) on preclinical models of murine HF-activation/regeneration results in accelerated anagen-progress, while treatment of wounds with Sit results in reduced expression of fibrosis markers, increased induction of anagen around wounds, and HF-regeneration in the wound center. These effects are associated with higher expression of Wnt-target Lef1, known to be required for HF-anagen (HF-activation)/regeneration. Sit-treatment decreases pro-fibrotic signaling in the skin, induce a differentiation trajectory of HF-cells, and activate Wnt-targets related to HF-activation/growth but not those supporting fibrosis. Taken together, our study demonstrates a role for DPP4 in HF biology and shows how DPP4i, currently used as oral medication to treat diabetes, could be repurposed into a topical treatment agent to potentially reverse HF-loss in alopecia and after injury.
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| Overall design |
Intradermal injection of Sitagliptin or PBS (conrol), 48 h after processing of the skin for scRNAseq
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/37236597/
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| Contributor(s) |
Helm M, Schmidt M, Del Duca E, Liu Y, Mortensen LS, Loui J, Zheng Y, Binder H, Guttman-Yassky E, Cotsarelis G, Simon JC, Ferrer RA |
| Citation(s) |
37236597 |
| Submission date |
Apr 25, 2023 |
| Last update date |
Aug 14, 2023 |
| Contact name |
Maria Schmidt |
| E-mail(s) |
schmidt@izbi.uni-leipzig.de
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| Organization name |
IZBI
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| Street address |
Härtelstr. 16-18
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| City |
Leipzig |
| ZIP/Postal code |
04170 |
| Country |
Germany |
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| Platforms (1) |
| GPL16173 |
Illumina HiScanSQ (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA961679 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE230514_RAW.tar |
161.5 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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