Related Experiment Video

Updated: Jul 5, 2025

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
07:37

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice

Published on: June 6, 2025

114

Mammalian STE20-like kinase 1 inhibits synoviocytes activation in rheumatoid arthritis through mitochondrial

Min Tan1,2, Jing Mao1,2, Jianxiong Zheng1,2

  • 1Department of Rheumatology, Lanzhou University Second Hospital, No. 82, Cui Ying Men Street, Lanzhou City, 730030, Gansu Province, People's Republic of China.

Inflammation Research : Official Journal of the European Histamine Research Society ... [Et Al.]
|January 24, 2024
PubMed
Abstract

Insights

Mammalian STE20-like kinase 1 (MST1) is down-regulated in rheumatoid arthritis (RA). Upregulating MST1 inhibits RA fibroblast-like synoviocytes, reducing inflammation and bone erosion by affecting mitochondrial function.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Mammalian STE20-like kinase 1 (MST1) regulates critical cellular processes like proliferation, differentiation, and apoptosis, implicating it in cancer and autoimmune diseases.
  • The specific role and molecular targets of MST1 in rheumatoid arthritis (RA) pathogenesis remain largely uncharacterized.

Purpose of the Study:

  • To investigate the function and downstream mechanisms of MST1 in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs).
  • To determine the therapeutic potential of modulating MST1 in an in vivo model of arthritis.

Main Methods:

  • Constructed RA-FLS models overexpressing MST1 using lentiviral transfection.
  • Assessed the impact of MST1 on RA-FLS apoptosis, migration, invasion, and inflammation in vitro.
  • Evaluated MST1's effects on synovial inflammation and bone destruction in a rat arthritis model induced by complete Freund's adjuvant.

Main Results:

  • MST1 expression is decreased in RA-FLSs; its upregulation suppresses RA-FLS survival, migration, invasion, and inflammation.
  • MST1 inhibits the SIRT3/mTOR signaling pathway, leading to reduced mitochondrial autophagy, increased mitochondrial fission, and subsequent mitochondrial dysfunction and apoptosis.
  • In vivo studies demonstrated that MST1 activation alleviates synovial inflammation and bone erosion.

Conclusions:

  • MST1 exerts a protective role in rheumatoid arthritis by inhibiting the SIRT3/mTOR axis.
  • This inhibition reduces mitochondrial autophagy and promotes mitochondrial fission, ultimately decreasing RA-FLS activity and mitigating disease severity.
  • MST1 represents a potential therapeutic target for managing rheumatoid arthritis.
Keywords:
Fibroblast-like synoviocytesMammalian STE20-like kinase 1Mitochondrial dysfunctionRheumatoid arthritisSIRT3/mTOR axis

More Related Videos

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness08:52

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness

Published on: March 18, 2022

3.0K
Author Spotlight: Evaluating Traditional Chinese Therapy for Ankylosing Spondylitis in Mice04:47

Author Spotlight: Evaluating Traditional Chinese Therapy for Ankylosing Spondylitis in Mice

Published on: October 27, 2023

979

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
8.9K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.5K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.0K