Kidney Week

Abstract: FR-PO920

Stromal Prorenin Receptor (PRR) Is Critical for Normal Kidney Development

Session Information

• Development, Stem Cells, Regenerative Medicine - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 501 Development, Stem Cells, and Regenerative Medicine: Basic

Authors

• Yosypiv, Ihor V., Tulane University, New Orleans, Louisiana, United States

Ihor V. Yosypiv,

• Sequeira Lopez, Maria Luisa S., University of Virginia, Charlottesville, Virginia, United States

Maria Luisa S. Sequeira Lopez,

• Song, Renfang, Tulane University, New Orleans, Louisiana, United States

Renfang Song,

Background

The transcription factor Foxd1, a specific marker of kidney stromal cells, is critical for normal kidney development. Global loss of the PRR, a receptor for renin and prorenin, is lethal in mice, indicating its essential role in embryonic development. Here, we investigated the role of the PRR in Foxd1+ stromal progenitors in mice.

Methods

Foxd1-eGFP-Cre⁺ mice were crossed with PRR^flox/flox mice. The resulting Foxd1^Cre+/PRR^flox/flox mice represent deletion of the PRR in Foxd1+ stromal progenitors (cKO). Control mice consisted of Foxd1^Cre-/PRR^flox/flox littermates (Con). Molecular marker analysis was performed by immunohistochemistry in kidneys on E17.5. Glomerular number was counted at P0 from 3 consecutive H&E-stained sections/kidney adjacent to the longitudinal midplane. Conscious systolic, diastolic and mean tail-cuff arterterial blood pressure (BP) was measured in heterozygous (Foxd1^PRR+/-) (Het, n=3) and Con (n=3) mice at 2 months of age using a Visitech BP2000 system (Visitech Systems, Apex, NC).

Results

cKO mice showed neonatal mortality. Although kidney weight did not differ in surviving cKO mice on P0, the number of glomeruli per kidney section was reduced in cKO compared with Con (39±3.7 vs. 68±2.3, p<0.001). Immunofluorescence showed reduced expression of stromal markers Foxd1 and Meis1, expansion of Six2+ nephron progenitors, reduced expression of Jag1, lack of WT1+ glomeruli in more differentiated nephrons, decrease in the expression of renin and of α-SMA in the developing interstitium in cKO kidneys. cKO mice had fewer and thinner intrarenal arteries and arterioles. Systolic, diastolic and mean BP did not differ in Het and Con mice (124±3.5 vs. 133±11, p=0.4; 69±3 vs. 68±5, p=0.9; 88±3 vs. 92±7, p=0.6).

Conclusion

We conclude that stromal PRR restricts excessive expansion of nephron progenitors, thereby promoting nephron differentiation. In addition, stromal PRR is crucial for the differentiation of renin-positive cells as well as smooth muscle and the proper formation of the renal arterial tree.