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| Status |
Public on Apr 02, 2022 |
| Title |
Lymphatic vessels drain monosodium urate and activate immunity in gouty arthritis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Gouty Arthritis (GA) is caused by urate deposition in the joint capsule, cartilage, bone, and surrounding tissues to trigger recurrent attacks of acute joint inflammation. However, the clearance mechanism of urate deposition is still not clear. We aimed to investigate whether lymphatics vessels can drain monosodium and involve in the immune process of GA.
Methods: Inguinal lymph nodes (LNs) in 4 normal volunteers and 4 patients with acute flare of GA were examined by ultrasound. Acute and chronic GA flare mouse models were established by intra-footpad administrations of monosodium urate (MSU) for 1 week or 1 month. Mice were treated with VEGFR-3 inhibitor or undergone popliteal lymph node (PLN) excision or PLN macrophage depletion. The severity of foot inflammation, lymphatic draining function, concentration of uric acid (UA), and macrophage population were examined. Macrophages were co-cultured with MSU-treated lymphatic endothelial cells (LECs) and differential gene expression of LECs was assessed by Agilent gene expression microarray.
Results: 1) Draining LNs were enlarged in patients with GA flare and GA mouse models. 2) The lymphatic function and structure were abnormal in GA mouse models. 3) Acute GA mice had elevated UA levels in draining LNs, but not in the serum, while chronic GA mice had elevated UA levels in both LNs and serum. 4) Blockade of VEGFR-3 reduced foot inflammation in chronic GA mice. 5) MSU induces pro-inflammatory polarization of macrophages by inducing LEC inflammation. 6) PLN local depletion of macrophages or removal of PLNs alleviated foot inflammation in GA.
Conclusions: Lymphatics drain MSU to the draining LNs to clear deposited urate in the distal extremity and induce LECs to stimulate macrophage pro-inflammatory response during GA. We have identified a novel mechanism about MSU clearance and pro-inflammatory macrophage activation, and provided possible therapeutic approach for GA.
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| Overall design |
Lymphatic endothelial cells (LECs) were seeded in 6-well for 24 h at 37°C. Then the cells were treated with PBS and 300μg/ml monosodium urate (MSU) for 24h, respectively. PBS treatment group was the control group, the other group was the MSU group. Every group had three samples.
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| Contributor(s) |
Liang Q, Chang J |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Apr 01, 2022 |
| Last update date |
Apr 03, 2022 |
| Contact name |
Junli Chang |
| E-mail(s) |
[email protected]
|
| Organization name |
Long hua Hospital
|
| Street address |
Wanping South Road 725
|
| City |
shanghai |
| ZIP/Postal code |
200032 |
| Country |
China |
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| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
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| Samples (6)
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| GSM5994514 |
Lymphatic endothelial cells_PBS_24 hour_rep1 |
| GSM5994515 |
Lymphatic endothelial cells_PBS_24 hour_rep2 |
| GSM5994516 |
Lymphatic endothelial cells_PBS_24 hour_rep3 |
| GSM5994517 |
Lymphatic endothelial cells_MSU_24 hour_rep1 |
| GSM5994518 |
Lymphatic endothelial cells_MSU_24 hour_rep2 |
| GSM5994519 |
Lymphatic endothelial cells_MSU_24 hour_rep3 |
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| Relations |
| BioProject |
PRJNA822357 |
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