Indoxyl Sulfate Induces Leukocyte-endothelial Interactions Through Up-regulation of ICAM-1 in Acute Kidney Injury
Study Details
Study Description
Brief Summary
Indoxyl sulfate (IS) is an anionic uremic toxin that is accumulated in the serum of patients with uremia. In previous study, the investigators successfully induced AKI animal model. IS enhanced intercellular adhesion molecule-1 (ICAM-1) expression in IL-1β-treated human umbilical vein endothelial cells (HUVECs) that this may play a critical role in the progression of AKI. However, the molecular mechanisms of ICAM-1 expression in IS-treated IL-1β-treated HUVECs need to be elucidated. HUVECs incubated with 0.2 or 1 mM IS for 24 h did not cause cytotoxicity. The IL-1β-induced ICAM-1 expression in HUVECs was significantly enhanced by IS pretreatment. Furthermore, the regulation of adhesion molecule expression involves a complex array of intracellular signaling pathways including mitogen-activated protein kinase (MAPKs), reactive oxygen species (ROS) and transcriptional factors. A better understanding of this might provide important insights into the prevention of AKI.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Over the past decade, acute kidney injury (AKI) has acquired much attention because of their potentially devastating problems in clinical medicine. When kidneys lost their filtering function, a lot of dangerous metabolites were accumulated in the body, including urea, nitrogenous waste products and uremic toxins. Indoxyl sulfate (IS) is an anionic uremic toxin that is accumulated in the serum of patients with uremia. In previous study, the investigators successfully induced AKI animal model. IS enhanced intercellular adhesion molecule-1 (ICAM-1) expression in IL-1β-treated human umbilical vein endothelial cells (HUVECs) that this may play a critical role in the progression of AKI. However, the molecular mechanisms of ICAM-1 expression in IS-treated IL-1β-treated HUVECs need to be elucidated. HUVECs incubated with 0.2 or 1 mM IS for 24 h did not cause cytotoxicity. The IL-1β-induced ICAM-1 expression in HUVECs was significantly enhanced by IS pretreatment. Furthermore, the regulation of adhesion molecule expression involves a complex array of intracellular signaling pathways including mitogen-activated protein kinase (MAPKs), reactive oxygen species (ROS) and transcriptional factors. A better understanding of this might provide important insights into the prevention of AKI.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Acute kidney injury Acute kidney injury in ICU |
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| Non acute kidney injury Non acute kidney injury |
Outcome Measures
Primary Outcome Measures
- Renal function recovery (BUN, Cre) [1 month]
Eligibility Criteria
Criteria
Inclusion Criteria:
- ICU patients
Exclusion Criteria:
- Less than 20 years old
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Taiwan University Hospital | Taipei | Taiwan | 100 |
Sponsors and Collaborators
- National Taiwan University Hospital
Investigators
- Principal Investigator: Yu-Hsiang Chou, MD, NTUH Yun-Lin branch
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 201310062RINA