Related Experiment Video
Updated: Jan 19, 2026
Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
Published on: March 24, 2017
Deficiency of inducible nitric oxide synthase alleviates dermal fibrosis and inflammation in scleroderma
Jing Luo1, Mingwei Li1, Di Zhao1
1Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin 300070, China.
Abstract:
Scleroderma is a connective tissue disorder marked by chronic inflammation and progressive skin fibrosis. Abnormal activation of fibroblasts (FBs) and deposition of collagen in the extracellular matrix (ECM) are the key to the progression of scleroderma. While FBs activation has been attributed to the dysfunction of keratinocytes (KCs) and immune cells, the crosstalk among these cells is considered critical for scleroderma progression. Recent evidence indicates that inducible nitric oxide synthase (iNOS) is highly expressed in scleroderma lesions, and iNOS contributes to the progression of dermatoses. Nevertheless, the specific role of iNOS in scleroderma remains to be fully elucidated. We utilized a bleomycin (BLM)-induced scleroderma model in wildtype (WT) and iNOS knockout (iNOS KO) mice to investigate the function of iNOS in scleroderma. We demonstrated that iNOS deficiency alleviated scleroderma progression, inhibiting inflammatory factor expression in KCs and neutrophils (Neus) infiltration. Subsequently, we stimulated FBs with TNF-α and IL-1β, which are mainly expressed by KCs and Neus, and confirmed that iNOS deletion attenuated FBs activation. We also revealed that iNOS inhibitors significantly attenuated the severity of scleroderma lesions. Our study collectively unveils a pivotal role of iNOS in scleroderma, highlighting its potential as a therapeutic target.
Insights
Inducible nitric oxide synthase (iNOS) drives scleroderma progression by activating fibroblasts and promoting inflammation. Inhibiting iNOS significantly reduced disease severity in a mouse model, suggesting iNOS as a therapeutic target.
Area of Science:
- Immunodermatology
- Fibrotic diseases
- Connective tissue disorders
Background:
- Scleroderma involves chronic inflammation and skin fibrosis due to fibroblast activation and collagen deposition.
- Cellular crosstalk between keratinocytes, immune cells, and fibroblasts is crucial in scleroderma pathogenesis.
- Inducible nitric oxide synthase (iNOS) is upregulated in scleroderma lesions, but its specific role is unclear.
Purpose of the Study:
- To elucidate the specific role of inducible nitric oxide synthase (iNOS) in the progression of scleroderma.
- To investigate the therapeutic potential of targeting iNOS in a scleroderma model.
Main Methods:
- Utilized a bleomycin-induced scleroderma mouse model comparing wildtype (WT) and iNOS knockout (iNOS KO) mice.
- Assessed inflammatory factor expression and immune cell infiltration (keratinocytes and neutrophils).
- Stimulated fibroblasts with TNF-α and IL-1β to evaluate the impact of iNOS deletion on fibroblast activation.
Main Results:
- iNOS deficiency significantly alleviated scleroderma progression, reducing inflammation and neutrophil infiltration.
- Deletion of iNOS attenuated fibroblast activation induced by keratinocyte- and neutrophil-derived factors.
- iNOS inhibitors demonstrated a significant reduction in scleroderma lesion severity.
Conclusions:
- Inducible nitric oxide synthase (iNOS) plays a pivotal role in driving scleroderma pathogenesis.
- Targeting iNOS presents a promising therapeutic strategy for managing scleroderma.
Related Concept Videos
01:28Nitric Oxide Signaling Pathway
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...