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  2. Research of STEAP3 interaction with Rab7A and RACK1 to modulate the MAPK and JAK/STAT signaling in Osteoarthritis

Research of STEAP3 interaction with Rab7A and RACK1 to modulate the MAPK and JAK/STAT signaling in Osteoarthritis

  • Int Immunopharmacol. 2023 Oct 9;124(Pt B):111034. doi: 10.1016/j.intimp.2023.111034.
Chang Sun 1 Song Peng 1 Zhongyang Lv 1 Ting Guo 1 Lei Zhang 2
Affiliations

Affiliations

  • 1 Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China.
  • 2 Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China. Electronic address: LeiZHANG1987MD@163.com.
Abstract

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. The molecular mechanisms underlying OA progression remain incompletely understood. In this study, we investigated the role of STEAP3 (Six Transmembrane Epithelial Antigen of the Prostate 3) in the development of OA. Our results demonstrated that STEAP3 was upregulated in OA cartilage tissues and contributes to the progression of the disease. To elucidate the mechanism, we employed transcriptomic and interaction proteomics analysis, and identified dysregulated genes and pathways associated with STEAP3 overexpression. Specifically, we found that STEAP3 interacted with Rab7A, a protein involved in intracellular trafficking and Autophagy, and suppressed its activity. In addition, STEAP3 interacted with activated C kinase 1 (RACK1) and enhanced its activity. Furthermore, our data indicated that the suppression of Rab7A activity by STEAP3 promoted the activation of Receptor Tyrosine Kinases (RTKs) and the promoting effects of RACK1 by STEAP3, both of which in turn activated the MAPK and JAK/STAT signaling pathways. In conclusion, our findings highlighted the role of STEAP3 in promoting OA progression. By inhibiting Rab7A activity and promoting RACK1 activity, STEAP3 enhanced inflammation through the activation of RTKs and subsequent activation of the MAPK and JAK/STAT signaling pathways. Targeting STEAP3 may provide a potential therapeutic strategy for the treatment of OA by modulating these interconnected pathways.

Keywords

JAK/STAT; MAPK; Osteoarthritis; RTK; Rab7A; STEAP3.

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