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PARP1 Inhibition as a Novel Therapeutic Target for Keloid Disease
Tae Hwan Park1, Chan Woo Kim1, Jin Sik Choi1
1Department of Plastic and Reconstructive Surgery, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea.
Abstract:
Objective: Inactivation of poly(ADP-ribose) polymerase 1 (PARP1) has been found to have protective effect in several fibrotic diseases. But the effect is not studied yet in keloids. Herein, we evaluated the therapeutic effect of PARP1 inhibitor, rucaparib, for keloids. Approach: The protein expressions of PARP1 and smad3 were evaluated with western blotting in keloids and controls. The effect of rucaparib was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and migration assay. We further analyzed the effect of rucaparib on patient-derived keloid xenograft murine model. Results: The protein expressions of PARP1 and smad3 were significantly higher in keloid tissue. Rucaparib (20 μM) significantly suppressed the proliferation of keloid fibroblasts. Moreover, the combination of rucaparib (20 μM) and triamcinolone (50 μM) showed additive suppressive effect on keloid fibroblasts. Migration assay showed that rucaparib (10 μM) significantly suppressed the migration of keloid fibroblasts. Fibrosis markers in keloid fibroblasts significantly decreased after rucaparib treatment (20 μM). In patient-derived keloid xenograft model, rucaparib significantly reduced the size of keloid tissue. Innovation and Conclusion: The study data suggest PARP1 might be a novel therapeutic target for keloid disease. PARP1 inhibitor, rucaparib, might be a promising therapeutic drug for the treatment of keloid disease.
Insights
Poly(ADP-ribose) polymerase 1 (PARP1) inhibition shows promise for keloid treatment. The PARP1 inhibitor rucaparib reduced keloid fibroblast proliferation and migration, suggesting PARP1 as a therapeutic target.
Area of Science:
- Dermatology
- Oncology
- Molecular Biology
Background:
- Poly(ADP-ribose) polymerase 1 (PARP1) inhibition demonstrates protective effects in fibrotic diseases.
- The therapeutic potential of PARP1 inhibition in keloid treatment remains unexplored.
Purpose of the Study:
- To evaluate the therapeutic efficacy of the PARP1 inhibitor rucaparib in keloids.
- To investigate PARP1 and smad3 protein expression in keloid tissues.
Main Methods:
- Western blotting was used to assess PARP1 and smad3 protein levels in keloid and control tissues.
- In vitro assays (MTT and migration assays) evaluated rucaparib's effects on keloid fibroblasts.
- A patient-derived keloid xenograft murine model was used to assess in vivo efficacy.
Main Results:
- PARP1 and smad3 protein expression were significantly elevated in keloid tissues.
- Rucaparib suppressed keloid fibroblast proliferation and migration.
- Rucaparib treatment reduced fibrosis markers and xenograft keloid size.
Conclusions:
- PARP1 is a potential novel therapeutic target for keloid disease.
- Rucaparib demonstrates promise as a therapeutic agent for treating keloids.
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