scholarly journals Tissue-specific deletion of Crry from mouse proximal tubular epithelial cells increases susceptibility to renal ischemia–reperfusion injury

2014 ◽  
Vol 86 (4) ◽  
pp. 726-737 ◽  
Author(s):  
Jing Miao ◽  
Allison M. Lesher ◽  
Takashi Miwa ◽  
Sayaka Sato ◽  
Damodar Gullipalli ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Tubular Epithelial Cells ◽  
Renal Ischemia Reperfusion Injury ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Specific Deletion

scholarly journals MO339KIDNEY DERIVED APOM AND ITS ROLE IN ACUTE KIDNEY INJURY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Line Stattau Bisgaard ◽  
Pernille M Christensen ◽  
Ernst-Martin Füchtbauer ◽  
Lars Bo Nielsen ◽  
Christina Christoffersen
Keyword(s):  
Acute Kidney Injury ◽  
Epithelial Cells ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Epithelial Cells ◽  
Wild Type ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular

Abstract Background and Aims Acute kidney injury is a severe disease with detrimental outcomes. The underlying ethiology is still elusive and besides dialysis, treatment options are poor. Apolipoprotein M (apoM) is mainly expressed in liver and in proximal tubular epithelial cells in the kidney. In plasma, apoM associates with HDL particles via a retained signal peptide. ApoM is a carrier of sphingosine-1-phosphate (S1P), a small bioactive lipid involved in e.g. angiogenesis, lymphocyte trafficking, and vascular barrier function. Recently, it was shown that apoM/S1P protects against development of liver and lung fibrosis. In urine, apoM is normally undetectable in both wild type mice and healthy humans. However, lack of megalin receptors in proximal tubuli induces loss of apoM into the urine. The biological function of kidney-derived apoM is unknown, but it has been hypothesized that apoM might be secreted to the pre-urine to sequester molecules, such as S1P, from secretion. The aim of this study was to unravel the role of apoM in kidney biology and in acute kidney injury. Method A novel kidney specific human apoM transgenic mouse (RPTEC-hapoMTG), was generated by expressing human apoM under the control of the proximal tubular epithelial cell specific Sglt2 promoter. The effect of kidney specific apoM overexpression on acute kidney injury was accessed by inducing either cisplatin or ischemia/reperfusion injury. Further, a stable cell line of HK-2 cells overexpressing hapoM (HK-2hapoM-TG) was generated and the cells were cultured on transwells to assess the secretion of apoM to respectively the apical and basolateral site. Results hapoM was present in plasma from RPTEC-hapoMTG mice (mean 0.18 μM), indicating that kidney-derived apoM can be secreted to plasma. When assessing the secretion of hapoM from proximal tubular epithelial cells in vitro, studies support that apoM can be secreted to both the apical (urine) and basolateral (blood) compartment. No differences in kidney injury markers (plasma urea and creatinine) between RPTEC-hapoMTG and wild type (WT) mice subjected to cisplatin injections, or in kidney injury score determined by histological evaluation was found. Similar, we could not detect any histological difference between RPTEC-hapoMTG and WT mice after ischemia/reperfusion injury, and overexpression of hapoM did not affect kidney gene expression of inflammatory markers (i.e. IL6, MCP-1) compared to WT mice. Conclusion Our study suggests that apoM can be secreted to both the apical and basolateral compartment, supporting a role for apoM in sequestering molecules from secretion in urine. Transgenic overexpression of apoM in proximal tubular epithelial cells of mice did not protect against acute kidney injury.

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