Glomerular Parietal Epithelial Cells Contribute to Adult Podocyte Regeneration in Experimental Focal Segmental Glomerulosclerosis

Kidney Int. 2015 Nov;88(5):999-1012. doi: 10.1038/ki.2015.152. Epub 2015 May 20.

Abstract

As adult podocytes cannot adequately proliferate following depletion in disease states, there has been interest in the potential role of progenitors in podocyte repair and regeneration. To determine whether parietal epithelial cells (PECs) can serve as adult podocyte progenitors following disease-induced podocyte depletion, PECs were permanently labeled in adult PEC-rtTA/LC1/R26 reporter mice. In normal mice, labeled PECs were confined to Bowman's capsule, whereas in disease (cytotoxic sheep anti-podocyte antibody) labeled PECs were found in the glomerular tuft in progressively higher numbers by days 7, 14, and 28. Early in disease, the majority of PECs in the tuft coexpressed CD44. By day 28, when podocyte numbers were significantly higher and disease severity was significantly lower, the majority of labeled PECs coexpressed podocyte proteins but not CD44. Neither labeled PECs on the tuft nor podocytes stained for the proliferation marker BrdU. The de novo expression of phospho-ERK colocalized to CD44 expressing PECs, but not to PECs expressing podocyte markers. Thus, in a mouse model of focal segmental glomerulosclerosis typified by abrupt podocyte depletion followed by regeneration, PECs undergo two phenotypic changes once they migrate to the glomerular tuft. Initially these cells are predominantly activated CD44 expressing cells coinciding with glomerulosclerosis, and later they predominantly exhibit a podocyte phenotype, which is likely reparative.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / etiology
  • Animals
  • Bowman Capsule / pathology
  • Cell Movement
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p57 / analysis
  • Disease Models, Animal
  • Epithelial Cells / chemistry
  • Epithelial Cells / physiology*
  • Glomerulosclerosis, Focal Segmental / complications
  • Glomerulosclerosis, Focal Segmental / metabolism
  • Glomerulosclerosis, Focal Segmental / pathology*
  • Hyaluronan Receptors / analysis
  • Intracellular Signaling Peptides and Proteins / analysis
  • MAP Kinase Signaling System
  • Membrane Proteins / analysis
  • Mice
  • Microfilament Proteins / analysis
  • Podocytes / chemistry
  • Podocytes / pathology
  • Podocytes / physiology*
  • Regeneration*
  • Stem Cells / physiology
  • beta-Galactosidase / metabolism

Substances

  • Cdkn1c protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p57
  • Hyaluronan Receptors
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • NPHS2 protein
  • Synpo protein, mouse
  • beta-Galactosidase