Abstract: SA-PO807
Genetic Depletion of Adenosine Kinase in Macrophage Aggravates Renal Fibrosis by Modulating M1/M2 Macrophage Polarization
Session Information
- Molecular Mechanisms of CKD - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 1903 CKD (Non-Dialysis): Mechanisms
Authors
- Xing, Chang Ying, First Affiliated Hospital of Nanjing Medical University, Nanjing, JIangSu, China
- Liu, Xi, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Yuan, Yanggang, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- An, Xiaofei, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, China
- Mao, Huijuan, First Affiliated Hospital of Nanjing Medical University, Nanjing, JIangSu, China
- Zhang, Bo, The first affiliated hosptial of Nanjing Medical University, Nanjing, China
Background
Renal fibrosis is a common pathological manifestation of chronic renal diseases to end-stage renal failure, regardless of the cause. Accumulating evidence suggests a
key role of macrophages in the pathogenesis of renal fibrosis. Adenosine (ADO) is an endogenous nucleotide involved in the energy metabolism and adenosine can be metabolized by adenosine kinase (ADK) or adenosine deaminase in cells. Adenosine can regulate the function of multiple immune cells. Therefore, we assume that the specific knockout of adenosine kinase gene can affect the function of macrophages and play a role in renal fibrosis.
Methods
12 wild-type adult male mice and 12 ADK-deficient adult male mice undergo a sham operation or a unilateral ureteral occlusion operation.14 days after surgery, the kidney cortex was preserved to investigate renal pathological changes and renal fibrosis extent. F4/80 immunofluorescence staining and immunohistochemical staining was used to detect the degree of macrophage infiltration and M1 and M2 macrophages respectively. in vitro, we investigate the effrct of ADKI to RAW264.7 macrophages.
Results
ADK-/- UUO group had more severe interstitial fibrosis than that in WT UUO group.Infiltrated macrophages in the ADK-/- UUO group were increased than the WT UUO group (P<0.05) and M2 macrophages were predominate.ADKI promoted the RAW264.7 macrophages migration (P<0.05) and increased M2 macrophages biomarker expression along with inhibiting pron of -inflammatory cytokines release.ADKI increased the basic oxygen demand and maximal oxygen consumption of macrophages and reduced the extracellular acidification rate compared with Contol group (P<0.05). The numbers of M2 macrophages were negatively correlated with eGFR.The numbers of macrophages infiltrated in patients of Class III and IV DN was significantly higher than Class IIa or IIb stage(P < 0.05). patients with more severe renal tubular injury and interstitial fibrosis had more M2 macrophage.
Conclusion
Genetic depletion of adenosine kinase of macrophage exacerbates UUO-induced fibrotic lesions by mediating macrophage migration and promoting M2 macrophages transformation. Inhibition of ADK promote the conversion of macrophages to M2 type by inhibiting the glycolytic pathway. the more severe renal damage in patients with DKD, the more macrophages infiltrate.
Funding
- Government Support - Non-U.S.