The Effects of Synthetic SREBP-1 and PPAR-γ Decoy Oligodeoxynucleotide on Acne-like Disease In Vivo and In Vitro via Lipogenic Regulation
Acne vulgaris has a pathogenesis that involves increased sebum production and perifollicular inflammation. Sterol regulatory element-binding protein-1 (SREBP-1) and peroxisome proliferator activated receptor-γ (PPAR-γ) are transcription factors that regulate numerous genes involved in lipid biosynth...
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MDPI AG
2022-12-01
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| Series: | Biomolecules |
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| author | Hyemin Gu Hyun-Jin An Mi-Gyeong Gwon Seongjae Bae Christos C. Zouboulis Kwan-Kyu Park |
| author_facet | Hyemin Gu Hyun-Jin An Mi-Gyeong Gwon Seongjae Bae Christos C. Zouboulis Kwan-Kyu Park |
| author_sort | Hyemin Gu |
| collection | DOAJ |
| description | Acne vulgaris has a pathogenesis that involves increased sebum production and perifollicular inflammation. Sterol regulatory element-binding protein-1 (SREBP-1) and peroxisome proliferator activated receptor-γ (PPAR-γ) are transcription factors that regulate numerous genes involved in lipid biosynthesis. To improve a new therapeutic approach, we designed the SREBP/PPAR decoy oligodeoxynucleotide (ODN), a synthetic short DNA containing complementary sequences for the SREBP and PPAR transcription factors. We aim to investigate the beneficial functions and the molecular mechanisms of the synthetic SREBP/PPAR decoy ODN in lipogenic models. <i>C. acnes</i> was intradermally injected with a 1.0 × 10<sup>7</sup> colony forming unit/20 μL. The synthetic SREBP/PPAR decoy ODN or scrambled decoy ODN (10 μg) was transferred via the mouse tail vein injection. SZ95 cells were transfected with 2 μg of synthetic ODNs. After transfection, the SZ95 cells were cultured in serum-free medium containing 20 ng/μL of insulin-like growth factor-1 (IGF)-1 for 24 h. To investigate the expression of gene and signaling pathways, we performed Western blotting. The distribution of the chimeric decoy ODN was confirmed by EMSA. Lipid levels were assessed by Nile red and Oil Red O staining. The cytokine levels were measured by ELISA kit. This study showed that <i>C. acnes</i>-injected mice and IGF-1-stimulated SZ95 cells exhibited increased expression of SREBP-1 and PPAR-γ compared to the normal controls. In contrast, the administration of the SREBP/PPAR chimeric decoy ODN significantly suppressed the upregulation of lipogenic genes. Furthermore, the SREBP/PPAR decoy ODN decreased the plasma cytokines and cytokine levels of total protein. These results suggested that the SREBP/PPAR decoy ODN exerts its anti-lipogenic effects by regulating lipid metabolism and by inhibiting lipogenesis through the inactivation of the SREBP and PPAR pathways. Therefore, the synthetic SREBP/PPAR ODN demonstrates substantial therapeutic feasibility for the treatment of acne vulgaris. |
| first_indexed | 2024-03-09T17:15:59Z |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T17:15:59Z |
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| spelling | doaj.art-24a9c69aa50f4a47996dc71be469acba2023-11-24T13:34:35ZengMDPI AGBiomolecules2218-273X2022-12-011212185810.3390/biom12121858The Effects of Synthetic SREBP-1 and PPAR-γ Decoy Oligodeoxynucleotide on Acne-like Disease In Vivo and In Vitro via Lipogenic RegulationHyemin Gu0Hyun-Jin An1Mi-Gyeong Gwon2Seongjae Bae3Christos C. Zouboulis4Kwan-Kyu Park5Department of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of KoreaDepartment of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of KoreaDepartment of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of KoreaDepartment of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of KoreaDepartments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Auenweg 38, 06847 Dessau, GermanyDepartment of Pathology, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of KoreaAcne vulgaris has a pathogenesis that involves increased sebum production and perifollicular inflammation. Sterol regulatory element-binding protein-1 (SREBP-1) and peroxisome proliferator activated receptor-γ (PPAR-γ) are transcription factors that regulate numerous genes involved in lipid biosynthesis. To improve a new therapeutic approach, we designed the SREBP/PPAR decoy oligodeoxynucleotide (ODN), a synthetic short DNA containing complementary sequences for the SREBP and PPAR transcription factors. We aim to investigate the beneficial functions and the molecular mechanisms of the synthetic SREBP/PPAR decoy ODN in lipogenic models. <i>C. acnes</i> was intradermally injected with a 1.0 × 10<sup>7</sup> colony forming unit/20 μL. The synthetic SREBP/PPAR decoy ODN or scrambled decoy ODN (10 μg) was transferred via the mouse tail vein injection. SZ95 cells were transfected with 2 μg of synthetic ODNs. After transfection, the SZ95 cells were cultured in serum-free medium containing 20 ng/μL of insulin-like growth factor-1 (IGF)-1 for 24 h. To investigate the expression of gene and signaling pathways, we performed Western blotting. The distribution of the chimeric decoy ODN was confirmed by EMSA. Lipid levels were assessed by Nile red and Oil Red O staining. The cytokine levels were measured by ELISA kit. This study showed that <i>C. acnes</i>-injected mice and IGF-1-stimulated SZ95 cells exhibited increased expression of SREBP-1 and PPAR-γ compared to the normal controls. In contrast, the administration of the SREBP/PPAR chimeric decoy ODN significantly suppressed the upregulation of lipogenic genes. Furthermore, the SREBP/PPAR decoy ODN decreased the plasma cytokines and cytokine levels of total protein. These results suggested that the SREBP/PPAR decoy ODN exerts its anti-lipogenic effects by regulating lipid metabolism and by inhibiting lipogenesis through the inactivation of the SREBP and PPAR pathways. Therefore, the synthetic SREBP/PPAR ODN demonstrates substantial therapeutic feasibility for the treatment of acne vulgaris.https://www.mdpi.com/2218-273X/12/12/1858decoy oligodeoxynucleotidelipogenic regulationperoxisome proliferator activated receptor-γsterol regulatory element-binding protein-1 |
| spellingShingle | Hyemin Gu Hyun-Jin An Mi-Gyeong Gwon Seongjae Bae Christos C. Zouboulis Kwan-Kyu Park The Effects of Synthetic SREBP-1 and PPAR-γ Decoy Oligodeoxynucleotide on Acne-like Disease In Vivo and In Vitro via Lipogenic Regulation Biomolecules decoy oligodeoxynucleotide lipogenic regulation peroxisome proliferator activated receptor-γ sterol regulatory element-binding protein-1 |
| title | The Effects of Synthetic SREBP-1 and PPAR-γ Decoy Oligodeoxynucleotide on Acne-like Disease In Vivo and In Vitro via Lipogenic Regulation |
| title_full | The Effects of Synthetic SREBP-1 and PPAR-γ Decoy Oligodeoxynucleotide on Acne-like Disease In Vivo and In Vitro via Lipogenic Regulation |
| title_fullStr | The Effects of Synthetic SREBP-1 and PPAR-γ Decoy Oligodeoxynucleotide on Acne-like Disease In Vivo and In Vitro via Lipogenic Regulation |
| title_full_unstemmed | The Effects of Synthetic SREBP-1 and PPAR-γ Decoy Oligodeoxynucleotide on Acne-like Disease In Vivo and In Vitro via Lipogenic Regulation |
| title_short | The Effects of Synthetic SREBP-1 and PPAR-γ Decoy Oligodeoxynucleotide on Acne-like Disease In Vivo and In Vitro via Lipogenic Regulation |
| title_sort | effects of synthetic srebp 1 and ppar γ decoy oligodeoxynucleotide on acne like disease in vivo and in vitro via lipogenic regulation |
| topic | decoy oligodeoxynucleotide lipogenic regulation peroxisome proliferator activated receptor-γ sterol regulatory element-binding protein-1 |
| url | https://www.mdpi.com/2218-273X/12/12/1858 |
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