Fuchs, Michaela A. A. and Schrankl, Julia and Leupold, Christina and Wagner, Charlotte and Kurtz, Armin and Broeker, Katharina A-E (2022) Intact prostaglandin signaling through EP2 and EP4 receptors in stromal progenitor cells is required for normal development of the renal cortex in mice. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 322 (3). F295-F307. ISSN 1931-857X, 1522-1466
Full text not available from this repository. (Request a copy)Abstract
Cyclooxygenase (Cox) inhibitors are known to have severe side effects during renal development. These consist of reduced renal function, underdeveloped subcapsular glomeruli, interstitial fibrosis, and thinner cortical tissue. Global genetic deletion of Cox-2 mimics the phenotype observed after application of Cox inhibitors. This study aimed to investigate which cell types express Cox-2 and prostaglandin E2 receptors and what functions are mediated through this pathway during renal development. Expression of EP2 and EP4 mRNA was detected by RNAscope mainly in descendants of FoxD1+ stromal progenitors; EP1 and EP3, on the other hand, were expressed in tubules. Cox-2 mRNA was detected in medullary interstitial cells and macula densa cells. Functional investigations were performed with a cell-specific approach to delete Cox-2, EP2, and EP4 in FoxD1+ stromal progenitor cells. Our data show that Cox-2 expression in macula densa cells is sufficient to drive renal development. Deletion of EP2 or EP4 in FoxD1+ cells had no functional effect on renal development. Codeletion of EP2 and EP4 in FoxD1+ stromal cells, however, led to severe glomerular defects and a strong decline of glomerular filtration rate (1.316 +/- 69.7 m./min/100 g body wt in controls vs. 644.1 +/- 64.58 m./min/100 g body wt in FoxD1+ /Cre EP2-/- EP4ff mice), similar to global deletion of Cox-2. Furthermore, EP2/EP4-deficient mice showed a significant increase in collagen production with a strong downregulation of renal renin expression. This study shows the distinct localization of EP receptors in mice. Functionally, we could identify EP2 and EP4 receptors in stromal FoxD1+ progenitor cells as essential receptor subtypes for normal renal development. NEW & NOTEWORTHY Cyclooxygenase-2 (Cox-2) produces prostaglandins that are essential for normal renal development. It is unclear in which cells Cox-2 and the receptors for prostaglandin E2 (EP receptors) are expressed during late nephrogenesis. This study identified the expression sites for EP subtypes and Cox-2 in neonatal mouse kidneys. Furthermore, it shows that stromal progenitor cells may require intact prostaglandin E2 signaling through EP2 and EP4 receptors for normal renal development.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RENIN-ANGIOTENSIN SYSTEM; KIDNEY; E-2; MOUSE; CYCLOOXYGENASE-2; DISRUPTION; LOCALIZATION; HYPERTENSION; EXPRESSION; DISCOVERY; cyclooxygenase-2; interstitial cells; prostaglandin receptors; renal development; renal function |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Oct 2023 09:21 |
| Last Modified: | 17 Oct 2023 09:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/56480 |
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