Ribosomal S6 Protein Kinase 2 Aggravates the Process of Systemic Scleroderma

  • J Invest Dermatol. 2022 Dec;142(12):3175-3183.e5. doi: 10.1016/j.jid.2022.06.020.
Mengying Jiang  1 ,  Jianan Wang  2 ,  Yingjie Shen  1 ,  Junjie Zhu  1 ,  Zhili Liu  1 ,  Wenjie Gong  1 ,  Ying Yu  1 ,  Siyi Zhang  1 ,  Xuan Zhou  3 ,  Shengqu He  1 ,  Yonghuan Song  4 ,  Zhongxin Zhu  1 ,  Litai Jin  1 ,  Weitao Cong  5
Affiliations
  • 1. School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
  • 2. Department of Pharmacy, Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No.2 Hospital), Ningbo, China.
  • 3. Ningbo First Hospital, Ningbo, China.
  • 4. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 5. School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China. Electronic address: [email protected].
PMID: 35853487 DOI: 10.1016/j.jid.2022.06.020
Abstract

Systemic sclerosis is a complex process of pathogenesis, and the contributions of inherited genes, infections, and chemicals remain largely unknown. In this study, we showed that p90 ribosomal S6 protein kinase 2 (RSK2) was selectively upregulated in fibrotic skin and fibroblasts treated with the profibrotic cytokine TGF-β. Moreover, knockout of RSK2 specifically in skin fibroblasts or pharmacological inhibition of RSK2 attenuated skin fibrosis in a mouse model. Mechanistically, RSK2 directly interacted with glycogen synthase kinase 3β in vivo and in vitro and thereby induced phosphorylation of glycogen synthase kinase 3β at Ser9 to inhibit ubiquitination and degradation of GLI1, which promoted fibroblast differentiation and skin fibrosis. Consequently, RSK2 plays an important role in the dermal skin of systemic sclerosis. These findings provided a potential therapeutic target for systemic sclerosis.

Products