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JAK1/STAT3 pathwaycooperates with TGF-β/Smad2/3 pathway to regulate TSLP and promote the resorption process of herniated disc / 中华骨科杂志
Chinese Journal of Orthopaedics ; (12): 734-742, 2020.
Article in Chinese | WPRIM | ID: wpr-869016
ABSTRACT

Objective:

Resorption can occur after lumbar disc herniation, and Thymic stromal lymphopoietin (TSLP) is considered to be a key factor mediating reabsorption. Studies have found that under the action of inflammatory factors like TNF-α, IL-6, etc,the expression of TSLP in intervertebral disc tissue was increased, and then mononuclear macrophage chemokine-1 (MCP-1) was induced to induce infiltration of macrophage to promote reabsorption. To determine the mechanism, we design the experiment to explore the mechanism of IL-6-mediated JAK/STAT pathway and TGF-β/Smad pathway to promote the reabsorption of intervertebral disc by regulating the expression of TSLP.

Methods:

Rat bone marrow mesenchymal stem cells (MSC) and rat nucleus pulposus cells (NPC) were cultured in vitro, treating the cells withrat IL-6 recombinant protein, STAT3inhibitor and Smad2/3 inhibitorrespectively, and use real-time quantitative PCR (qRT-PCR) technology to detect the expression of JAK1, STAT3, Smad2, TSLP mRNA under different conditions; Western blot to detect the expression of TSLP, Smad2 and phosphate STAT3 protein; using enzyme-linked immunosorbent assay (Elisa) to detect the expression of TGF-β in two rat cells under the treatment of IL-6.

Results:

After stimulation ofIL-6 (10 ng/ml or 100 ng/ml) the expression of JAK1in MSC (10 ng/ml 5.13±1.21; 100 ng/ml 5.23±0.35; control group 0.97±0.03), STAT3 (10 ng/ml 6.50±0.38; 100 ng/ml 6.74±0.61; control group 0.87±0.19) was significantly increased, and TSLP also showed high expression in MSC (10 ng/ml 4.26±0.38; 100 ng/ml 5.05±0.46; control group 1.04±0.04).The expression of STAT3 (10 ng/ml 2.91±0.08; control group 1.12±0.11), TSLP (10 ng/ml 7.32±0.37; control group 1.03±0.03) in NPC also increased. After stimulation of IL-6, the expression of Smad2 increasing in MSC was observed (10 ng/ml 15.92±0.62; 100 ng/ml 20.28±0.58; control group 0.96±0.08), and increased expression of Smad2 in NPC (10 ng/ml 5.01±0.17; control group 0.96±0.03). The expression of TSLP in MSC decreased after adding STAT3 inhibitor (BP group, BP group 0.17±0.01; control group 0.90±0.09), the expression of TSLP also decreased in NPC (BP group 0.42±0.11; control group 0.90±0.11). After adding Smad2/3 inhibitor (SB group), the expression of TSLP in MSC decreased (SB group 0.33±0.01; control group 1.02±0.02), and the expression of TSLP in NPC also decreased (SB group 0.40±0.04; control group 0.99±0.01).

Conclusion:

IL-6 up-regulates TSLP expression via the JAK1/STAT3 signaling pathway and promotes prominent intervertebral disc reabsorption. At the same time, IL-6 can activate the TGF-β/Smad2/3 pathway and up-regulate the expression of TSLP, which play a synergistic role in the reabsorption process.
Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Orthopaedics Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Orthopaedics Year: 2020 Type: Article