Abstract: TH-PO109
Trib1 Is Involved in Renal Recovery and Regeneration in a Mouse Model of Ischemia/Reperfusion Injury
Session Information
- AKI: Inflammation, New Technologies, Omics
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Xie, Xiangcheng, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, ZHEJIANG, China
- Wang, Ming, Hangzhou First People''s Hospital,, Hangzhou, China
- Yang, Xiu, Hangzhou First People''s Hospital, Hangzhou, China
- Wei, Wei, Hangzhou First People?s Hospital, Hangzhou, China
Background
Acute kidney injury (AKI) is one of the most common serious complications in hospitalized patients. Despite tremendous effort has been made, AKI is still strongly associated with poor outcomes. Maladaptive repair after AKI exhibit a persistently increased risk of progression to chronic kidney disease (CKD). Macrophages are implicated in the initial injury after ischemic/reperfusion (I/R) and also participate in tubular repair after I/R. Macrophages are classified into two subsets, M1 (inflammatory) and M2 (anti-inflammatory). M1 macrophages play a pathogenic role in boosting inflammatory and kidney injury, whereas M2 macrophages exhibit an anti-inflammatory and wound healing. Evidence demonstrates that macrophage polarization plays a critical role in the process of kidney recovery and chronic fibrosis, hence, enhancement of M1 to M2 phenotype transition might promote renal recovery after I/R. Trib1 is critical for the differentiation of macrophages, therefore, we aimed to investigate the role of trib1 in the process of kidney recovery following I/R and the link between trib1 and macrophage phenotype.
Methods
We used lentiviral vector mediated RNA interfering (RNAi) to knock down expression of trib1 in mice to investigate the role of trib1 in the process of renal repair.
Results
Our results showed that mice with down regulation of trib1 showed markedly reduced renal function, severe renal pathological damage, and exacerbated inflammation. Inhibition the expression of trib1 resulted in an impaired ability to form M2 macrophages in the kidney, whereas coincided with increased M1 macrophages. Expression of TNF-α, IL-6, and IL-12 increased markedly in the trib1 suppressed mice accompanied with a decreased expression of IL-4 and IL-10. Inhibition of Trib1 led to reduced PCNA and Ki67-positive proliferating tubular cells.
Conclusion
Our results showed that trib1 is involved in kidney recovery and regeneration through the regulation of macrophage polarization. This might be a viable therapeutic option to enhance renal repair after I/R injury.
Funding
- Government Support - Non-U.S.