Relevance of von Hippel-Lindau protein for differentiation of renal renin expressing cells

• Applicant: Professor Dr. Armin Kurtz
• Subject Area: Anatomy and Physiology ; Nephrology
• Term: from 2013 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 240531172

• Final Report Year: 2023

Final Report Abstract

Juxtaglomerular renin-forming cells of the kidneys are considered to be highly specialized endocrine cells. The research project showed that prolonged activation of the hypoxia-induced signaling pathway induces metaplasia of juxtaglomerular reninforming cells into erythropoietin-forming cells. The project showed that in addition to juxtaglomerular cells, tubulointerstitial cells also express renin and that EPO expression can also be induced in these cells, with EPO induction being faster and easier than in the juxtaglomerular cells. The juxtaglomerular cells seem to protect their renin phenotype in hypoxic conditions by a stronger expression of prolyl-hydroxylases (especially PHD3). In progenitor cells (preglomerular vascular smooth muscle cells) of juxtaglomerular renin cells, activation of the hypoxia-induced signaling pathway leads to EPO induction only when the progenitor cells are triggered towards renin-expressing cells. However,they then express EPO instead of renin. In summary, the project has provided novel and exciting findings on the endocrine plasticity of mesenchymal kidney cells.

Publications

• Inhibition of transforming growth factor β1 signaling in resident interstitial cells attenuates profibrotic gene expression and preserves erythropoietin production during experimental kidney fibrosis in mice. Kidney International, 100(1), 122-137.
  Fuchs, Michaela A.A.; Broeker, Katharina A.E.; Schrankl, Julia; Burzlaff, Nicolai; Willam, Carsten; Wagner, Charlotte & Kurtz, Armin
  
• Localization of angiotensin II type 1 receptor gene expression in rodent and human kidneys. American Journal of Physiology-Renal Physiology, 320(4),F644-F653.
  Schrankl, Julia; Fuchs, Michaela; Broeker, Katharina; Daniel, Christoph; Kurtz, Armin & Wagner, Charlotte
  
• Prolyl‐4‐hydroxylases 2 and 3 control erythropoietin production in renin‐expressing cells of mouse kidneys. The Journal of Physiology, 600(3), 671-694.
  Broeker, Katharina A. E.; Fuchs, Michaela A. A.; Schrankl, Julia; Lehrmann, Claudia; Schley, Gunnar; Todorov, Vladimir T.; Hugo, Christian; Wagner, Charlotte & Kurtz, Armin
  
• Flexible and multifaceted: the plasticity of renin-expressing cells. Pflügers Archiv - European Journal of Physiology, 474(8), 799-812.
  Broeker, Katharina A. E.; Schrankl, Julia; Fuchs, Michaela A. A. & Kurtz, Armin
  
• Localization and characterization of proenkephalin-A as a potential biomarker for kidney disease in murine and human kidneys. Biomarkers, 28(1), 76-86.
  Fuchs, Michaela Alexandra Anna; Schrankl, Julia; Wagner, Charlotte; Daniel, Christoph; Kurtz, Armin & Broeker, Katharina Anna-Elisabeth
  
• The fate of erythropoietin-producing cells: another piece of the puzzle. Kidney International, 102(2), 230-233.
  Fuchs, Michaela A.A. & Kurtz, Armin