The origin of interstitial myofibroblasts in chronic kidney disease

Ivica Grgic1, Jeremy S Duffield, Benjamin D Humphreys

  • 1Renal Division, Brigham and Women's Hospital, Harvard Institutes of Medicine Rm 550, Boston, MA 02115, USA.

Insights

New research challenges the epithelial-to-mesenchymal transition (EMT) theory in kidney fibrosis. Findings suggest pericytes, not injured epithelial cells, are the primary source of myofibroblasts in chronic kidney disease (CKD).

Area of Science:

  • Nephrology
  • Cell Biology
  • Fibrosis Research

Background:

  • Chronic kidney diseases (CKD) cause irreversible renal parenchyma loss, characterized by tubulointerstitial fibrosis.
  • Myofibroblasts drive excessive matrix deposition in renal pathology.
  • Identifying myofibroblast origins is crucial for therapeutic strategies in fibrotic kidney disease.

Purpose of the Study:

  • To investigate the cellular origins of myofibroblasts in kidney fibrosis.
  • To critically evaluate the role of epithelial-to-mesenchymal transition (EMT) in myofibroblast recruitment in vivo.
  • To review recent findings from genetic fate mapping studies in kidney fibrosis models.

Main Methods:

  • Review of recent scientific literature.
  • Analysis of genetic fate mapping techniques in mouse models of kidney fibrosis.
  • Comparative analysis of cellular origins of myofibroblasts.

Main Results:

  • Recent genetic fate mapping studies cast doubt on EMT as a significant source of myofibroblasts in vivo.
  • Evidence points towards resident pericytes/perivascular fibroblasts as the primary myofibroblast progenitor pool.
  • The traditional view of resident fibroblasts as the sole precursor is also challenged.

Conclusions:

  • EMT is unlikely to be a direct contributor to the kidney myofibroblast population in vivo.
  • Pericytes and perivascular fibroblasts are identified as key progenitors of myofibroblasts in fibrotic kidney disease.
  • Genetic fate mapping is a powerful tool for understanding kidney homeostasis and disease mechanisms.

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