Related Experiment Video
Updated: Jun 18, 2026
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
MS80, a novel sulfated polysaccharide, inhibits CD40-NF-kappaB pathway via targeting RIP2
Xiaoguang Du1, Shan Jiang, Hongchun Liu
1Department of Molecular Pharmacology, School of Medicine and Pharmacy, Ocean University of China, Qingdao, People's Republic of China.
Abstract:
In the previous studies, MS80 was found to be able to inhibit the pulmonary fibrosis. However, the target of MS80 remains unclear. To determine the target and the antifibrosis mechanisms of MS80, affinity column, MALDITOF-MS/MS, co-immunoprecipitation, and co-localization were used. The results showed that MS80 targeting protein was receptor interacting protein 2 (RIP2), which was further confirmed by co-immunoprecipitation and co-localization. Moreover, MS80 inhibited the CD40 ligation-induced NF-kappaB activation, and subsequently inflammatory cytokines secretion, the collagen synthesis, and the excessive proliferation of fibroblasts. Thus the detailed molecular machinery was ascribed to the involvement of MS80 in targeting CD40 signal pathway via binding and blocking RIP2, the key component of CD40 signal transduction. The findings addressed here may substantially account for the effects of MS80 in combating the pulmonary fibrosis.
Insights
MS80 inhibits pulmonary fibrosis by targeting receptor interacting protein 2 (RIP2). This blocks the CD40 signaling pathway, reducing inflammation and fibroblast proliferation, offering a new therapeutic strategy for fibrosis.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Pulmonary fibrosis is a debilitating condition with limited treatment options.
- MS80 has shown potential in inhibiting pulmonary fibrosis, but its molecular target and mechanism were unknown.
Purpose of the Study:
- To identify the specific molecular target of MS80.
- To elucidate the antifibrotic mechanisms of MS80 at the molecular level.
Main Methods:
- Affinity chromatography and mass spectrometry (MALDITOF-MS/MS) were employed to identify MS80's binding protein.
- Co-immunoprecipitation and co-localization assays confirmed the interaction between MS80 and its target.
- Experiments assessed the impact of MS80 on CD40 signaling, NF-kappaB activation, and fibroblast behavior.
Main Results:
- Receptor interacting protein 2 (RIP2) was identified as the direct target of MS80.
- MS80 binding to RIP2 effectively inhibited CD40 ligation-induced NF-kappaB activation.
- MS80 significantly reduced inflammatory cytokine secretion, collagen synthesis, and fibroblast proliferation.
Conclusions:
- MS80 combats pulmonary fibrosis by targeting RIP2 within the CD40 signaling pathway.
- Blocking RIP2 disrupts downstream signaling, thereby mitigating key fibrotic processes.
- These findings provide a mechanistic basis for MS80's antifibrotic effects and suggest its therapeutic potential.
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...