Kidney Week

Abstract: TH-PO805

Epithelial Membrane Protein 2 (EMP2) Is Predominantly Expressed in Vascular Smooth Muscle Cells of the Kidney

Session Information

• Genetic Diseases of the Kidney - I
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Donnan, Michael D., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Michael D. Donnan,

• Scott, Rizaldy P., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Rizaldy P. Scott,

• Onay, Tuncer, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Tuncer Onay,

• Tarjus, Antoine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Antoine Tarjus,

• Onay, Ummiye venus, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Ummiye venus Onay,

• Quaggin, Susan E., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Susan E. Quaggin,

Background

Mutations in human gene Epithelial Membrane Protein 2 (EMP2) have been linked to childhood-onset nephrotic syndrome. However, we have previously reported that loss of Emp2 in mice does not cause nephrotic syndrome and that Emp2 lacks notable expression in podocytes or the glomerulus. Instead, we find that Emp2 has a distinctive vascular pattern of expression in multiple tissues including the kidney. As Emp2 is currently being investigated as a novel target for treatment of pathologic neovascularization and vasculo-proliferative diseases such as diabetes, we studied in detail the vascular expression of Emp2 across different organs as well as the kidneys.

Methods

We created a conditional floxed Emp2 allele carrying a lacZ cassette that allows whole-mount β-galactosidase (β-gal) histochemical analysis of Emp2 expression. Tissues were evaluated as whole mount and additionally embedded in OCT and cryosectioned for immunohistochemical analysis. We created endothelial-specific knockout mice by breeding floxed Emp2 animals with a Cdh5-Cre/ERT2 driver strain. Emp2 mRNA was profiled in various tissues using qRT-PCR analysis.

Results

Expression of Emp2 by β-gal histochemistry was seen in the arterial vasculature of multiple tissues including the kidney. Within the kidney, β-gal activity is localized to renal arterial vessels where it is expressed in Tagln⁺ (SM22a⁺) vascular smooth muscle cells and is absent in Podxl⁺ arterial endothelial cells, Emcn⁺ renal veins and glomerular endothelial cells. Emp2 expression within the kidney is unchanged upon endothelial specific knockout of the Emp2 gene consistent with the lack of β-gal activity in the endothelial cells of Emp2^lacZ reporter mice.

Conclusion

Our analysis reveals that Emp2 expression is largely confined to vascular smooth muscle cells of the arterial vasculature in the kidneys as well as multiple other organs. These findings provide important insights into the specific site of action of therapeutics designed to target Emp2.

Funding

• NIDDK Support