The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis
Abstract Background Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the different...
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Cellular & Molecular Biology Letters |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11658-023-00467-4 |
| _version_ | 1797769442902409216 |
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| author | Tao Yang Renyi Hei Xiaosong Li Tianhua Ma Yifen Shen Chao Liu Wen He Lin Zhu Yongchun Gu Yanping Hu Wenbin Wei Yihang Shen |
| author_facet | Tao Yang Renyi Hei Xiaosong Li Tianhua Ma Yifen Shen Chao Liu Wen He Lin Zhu Yongchun Gu Yanping Hu Wenbin Wei Yihang Shen |
| author_sort | Tao Yang |
| collection | DOAJ |
| description | Abstract Background Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the differentiation, development and proliferation of SGs is far away to fully understand. Methods Herein, the rat volar and mammary tissues with abundant SGs from female SD rats with (post-natal day (PND)-35) and without puberty onset (PND-25) were arrested, and conducted RNA sequencing. The protein complex of Neuropeptide Y receptor Y2 (NPY2R)/NPY5R/Nuclear factor of activated T cells 1 (NFATc1) was performed by immunoprecipitation, mass spectrum and gel filtration. Genome-wide occupancy of NFATc1 was measured by chromatin immunoprecipitation sequencing. Target proteins’ expression and localization was detected by western blot and immunofluorescence. Results NPY2R gene was significantly up-regulated in volar and mammary SGs of PND-25. A special protein complex of NPY2R/NPY5R/NFATc1 in PND-25. NFATc1 was dephosphorylated and activated, then localized into nucleus to exert as a transcription factor in volar SGs of PND-35. NFATc1 was especially binding at enhancer regions to facilitate the distal SG and sebum related genes’ transcription. Dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) contributed to NFATc1 phosphorylation in PND-25, and inactivated of DYRK1A resulted in NFATc1 dephosphorylation and nuclear localization in PND-35. Conclusions Our findings unmask the new role of NPY2R/NFATc1/DYRK1A in pubertal SG, and are of benefit to advanced understanding the molecular mechanism of SGs’ function after puberty, and provide some theoretical basis for the treatment of acne vulgaris from the perspective of hormone regulation. Graphical Abstract |
| first_indexed | 2024-03-12T21:08:04Z |
| format | Article |
| id | doaj.art-77e9a5d2019744cda817e3024f75eac3 |
| institution | Directory Open Access Journal |
| issn | 1689-1392 |
| language | English |
| last_indexed | 2024-03-12T21:08:04Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
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| series | Cellular & Molecular Biology Letters |
| spelling | doaj.art-77e9a5d2019744cda817e3024f75eac32023-07-30T11:20:24ZengBMCCellular & Molecular Biology Letters1689-13922023-07-0128111510.1186/s11658-023-00467-4The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesisTao Yang0Renyi Hei1Xiaosong Li2Tianhua Ma3Yifen Shen4Chao Liu5Wen He6Lin Zhu7Yongchun Gu8Yanping Hu9Wenbin Wei10Yihang Shen11Department of Medical Cosmetology, Suzhou Ninth People’s HospitalDepartment of Otolaryngology-Head and Neck Surgery, General Hospital of Shenyang Military Area CommandDepartment of Anorectal Surgery, Suzhou Ninth People’s HospitalGraduate School of Soochow UniversityCentral Laboratory, Suzhou Ninth People’s HospitalCentral Laboratory, Suzhou Ninth People’s HospitalCentral Laboratory, Suzhou Ninth People’s HospitalCentral Laboratory, Suzhou Ninth People’s HospitalCentral Laboratory, Suzhou Ninth People’s HospitalDepartment of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer HospitalDepartment of Oral Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of StomatologyCentral Laboratory, Suzhou Ninth People’s HospitalAbstract Background Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the differentiation, development and proliferation of SGs is far away to fully understand. Methods Herein, the rat volar and mammary tissues with abundant SGs from female SD rats with (post-natal day (PND)-35) and without puberty onset (PND-25) were arrested, and conducted RNA sequencing. The protein complex of Neuropeptide Y receptor Y2 (NPY2R)/NPY5R/Nuclear factor of activated T cells 1 (NFATc1) was performed by immunoprecipitation, mass spectrum and gel filtration. Genome-wide occupancy of NFATc1 was measured by chromatin immunoprecipitation sequencing. Target proteins’ expression and localization was detected by western blot and immunofluorescence. Results NPY2R gene was significantly up-regulated in volar and mammary SGs of PND-25. A special protein complex of NPY2R/NPY5R/NFATc1 in PND-25. NFATc1 was dephosphorylated and activated, then localized into nucleus to exert as a transcription factor in volar SGs of PND-35. NFATc1 was especially binding at enhancer regions to facilitate the distal SG and sebum related genes’ transcription. Dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) contributed to NFATc1 phosphorylation in PND-25, and inactivated of DYRK1A resulted in NFATc1 dephosphorylation and nuclear localization in PND-35. Conclusions Our findings unmask the new role of NPY2R/NFATc1/DYRK1A in pubertal SG, and are of benefit to advanced understanding the molecular mechanism of SGs’ function after puberty, and provide some theoretical basis for the treatment of acne vulgaris from the perspective of hormone regulation. Graphical Abstracthttps://doi.org/10.1186/s11658-023-00467-4Sebaceous glandsNPY2RNPY5RNFATc1DYRK1APuberty onset |
| spellingShingle | Tao Yang Renyi Hei Xiaosong Li Tianhua Ma Yifen Shen Chao Liu Wen He Lin Zhu Yongchun Gu Yanping Hu Wenbin Wei Yihang Shen The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis Cellular & Molecular Biology Letters Sebaceous glands NPY2R NPY5R NFATc1 DYRK1A Puberty onset |
| title | The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis |
| title_full | The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis |
| title_fullStr | The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis |
| title_full_unstemmed | The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis |
| title_short | The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis |
| title_sort | role of npy2r nfatc1 dyrk1a regulatory axis in sebaceous glands for sebum synthesis |
| topic | Sebaceous glands NPY2R NPY5R NFATc1 DYRK1A Puberty onset |
| url | https://doi.org/10.1186/s11658-023-00467-4 |
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