Podocyte-derived microparticles promote proximal tubule fibrotic signaling via p38 MAPK and CD36

Related Experiment Video

Updated: Feb 14, 2026

Isolation of Primary Human Proximal Tubule Epithelial Cells and Their Use in Creating a Microphysiological Model of the Renal Proximal Tubule
07:06

Isolation of Primary Human Proximal Tubule Epithelial Cells and Their Use in Creating a Microphysiological Model of the Renal Proximal Tubule

Published on: May 9, 2025

867

Mercedes N Munkonda1, Shareef Akbari1, Chloe Landry1

  • 1Kidney Research Centre, The Ottawa Hospital Research Institute, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.

Journal of Extracellular Vesicles
|February 14, 2018
PubMed

Insights

Podocyte microparticles (MPs) from injured kidney cells promote tubular fibrosis in diabetic kidney disease. These MPs activate signaling pathways in tubule cells, leading to extracellular matrix deposition and worsening kidney function.

Area of Science:

  • Nephrology
  • Cell Biology
  • Biochemistry

Background:

  • Tubulointerstitial fibrosis is a key feature of advanced diabetic kidney disease, contributing to renal function decline.
  • The precise mechanisms driving tubulointerstitial fibrosis remain incompletely understood.
  • Microparticles (MPs), vesicles from injured cells, are involved in intercellular signaling and have been observed in diabetes models and patients.

Purpose of the Study:

  • To investigate the role of podocyte-derived microparticles (MPs) in inducing fibrotic responses in tubular epithelial cells.
  • To elucidate the signaling pathways and molecular mechanisms by which podocyte MPs affect tubular cells.

Main Methods:

  • Human podocytes (hPODs) were cultured, and MPs were isolated from their media.
  • Human proximal tubule epithelial cells (PTECs) were treated with podocyte MPs.
  • Inhibitors for p38 MAPK (SB202190), TGF-β receptor (LY2109761), and the scavenger receptor CD36 were used to block specific pathways.
  • Western blotting and protein expression analysis were performed to assess signaling activation and extracellular matrix (ECM) production.

Main Results:

  • Podocyte MPs increased phosphorylation of p38 and Smad3 in PTECs.
  • Treatment with podocyte MPs led to increased expression of ECM proteins fibronectin and collagen type IV.
  • Inhibition of p38 MAPK partially attenuated MP-induced responses.
  • TGF-β receptor inhibition blocked Smad3 activation and ECM production, indicating downstream effects.
  • Blockade of CD36 completely prevented MP-induced p38 phosphorylation, Smad3 activation, and ECM production.

Conclusions:

  • Podocyte MPs interact with proximal tubule cells and trigger pro-fibrotic signaling cascades.
  • The CD36 scavenger receptor plays a critical role in mediating the pro-fibrotic effects of podocyte MPs.
  • These findings suggest that podocyte MPs may contribute to the pathogenesis of tubular fibrosis in glomerular diseases, including diabetic kidney disease.
Keywords:
CD36Extracellular vesiclesTGF-βepithelial cellsfibrosismicroparticlespodocytesproximal tubule

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