2. Academic Validation
  3. The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis

The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis

  • Cell Mol Biol Lett. 2023 Jul 27;28(1):60. doi: 10.1186/s11658-023-00467-4.
Tao Yang # 1,  Renyi Hei # 2,  Xiaosong Li # 3,  Tianhua Ma 4,  Yifen Shen 5,  Chao Liu 5,  Wen He 5,  Lin Zhu 5,  Yongchun Gu 5,  Yanping Hu 6,  Wenbin Wei 7,  Yihang Shen 8
Affiliations

Affiliations

  • 1 Department of Medical Cosmetology, Suzhou Ninth People's Hospital, Suzhou, 215200, Jiangsu, China.
  • 2 Department of Otolaryngology-Head and Neck Surgery, General Hospital of Shenyang Military Area Command, Shenyang, 110016, Liaoning, China.
  • 3 Department of Anorectal Surgery, Suzhou Ninth People's Hospital, Suzhou, 215200, Jiangsu, China.
  • 4 Graduate School of Soochow University, Suzhou, 215031, Jiangsu, China.
  • 5 Central Laboratory, Suzhou Ninth People's Hospital, 2666, Ludang Road, Suzhou, 215200, Jiangsu, China.
  • 6 Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450008, Henan, China.
  • 7 Department 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 Stomatology, No. 639 Zhizaoju Road, Huangpu District, Shanghai, 200013, China. tian_qian_cool@126.com.
  • 8 Central Laboratory, Suzhou Ninth People's Hospital, 2666, Ludang Road, Suzhou, 215200, Jiangsu, China. devbrother@sjtu.edu.cn.
  • # Contributed equally.
PMID: 37501148 DOI: 10.1186/s11658-023-00467-4
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.

Keywords

DYRK1A; NFATc1; NPY2R; NPY5R; Puberty onset; Sebaceous glands.

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