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Kidney derived apolipoprotein M and its role in acute kidney injury
Line S Bisgaard1,2, Pernille M Christensen1,2, Jeongah Oh3
1Department of Clinical Biochemistry, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Abstract:
Aim: 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 and carries sphingosine-1-phosphate (S1P), a small bioactive lipid. ApoM is undetectable in urine from healthy individuals but lack of megalin receptors in proximal tubuli cells induces loss of apoM into the urine. Besides this, very little is known about kidney-derived apoM. The aim of this study was to address the role of apoM in kidney biology and in acute kidney injury. Methods: A novel kidney-specific human apoM transgenic mouse model (RPTEC-hapoMTG) was generated and subjected to either cisplatin or ischemia/reperfusion injury. Further, a stable transfection of HK-2 cells overexpressing human apoM (HK-2-hapoMTG) was developed to study the pattern of apoM secretion in proximal tubuli cells. Results: Human apoM was present in plasma from RPTEC-hapoMTG mice (mean 0.18 μM), with a significant increase in plasma S1P levels. In vitro apoM was secreted to both the apical (urine) and basolateral (blood) compartment from proximal tubular epithelial cells. However, no differences in kidney injury score was seen between RPTEC-hapoMTG and wild type (WT) mice upon kidney injury. Further, gene expression of inflammatory markers (i.e., IL6, MCP-1) was similar upon ischemia/reperfusion injury. Conclusion: Our study suggests that kidney-derived apoM is secreted to plasma, supporting a role for apoM in sequestering molecules from excretion in urine. However, overexpression of human apoM in the kidney did not protect against acute kidney injury.
Insights
Kidney-derived apolipoprotein M (apoM) is secreted into plasma, potentially preventing urinary loss of molecules. However, kidney-specific apoM overexpression did not protect against acute kidney injury in mice.
Area of Science:
- Nephrology
- Biochemistry
- Molecular Biology
Background:
- Apolipoprotein M (apoM) is primarily found in the liver and kidney proximal tubules.
- In plasma, apoM binds HDL particles and transports sphingosine-1-phosphate (S1P).
- Kidney-derived apoM is typically undetectable in urine but can be lost due to megalin receptor deficiency.
Purpose of the Study:
- To investigate the role of apoM in kidney biology.
- To examine the function of kidney-derived apoM in acute kidney injury (AKI).
Main Methods:
- Generated a kidney-specific human apoM transgenic mouse model (RPTEC-hapoMTG).
- Induced AKI using cisplatin or ischemia/reperfusion.
- Utilized human proximal tubular epithelial cells (HK-2) overexpressing apoM for in vitro studies.
Main Results:
- Human apoM was detected in plasma of transgenic mice, with elevated S1P levels.
- In vitro, apoM was secreted apically (urine) and basolaterally (blood) from proximal tubular cells.
- No significant difference in kidney injury scores or inflammatory markers between transgenic and wild-type mice post-AKI.
Conclusions:
- Kidney-derived apoM is secreted into the plasma, suggesting a role in retaining molecules from urinary excretion.
- Overexpression of apoM in the kidney did not confer protection against experimental AKI.
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