The role of the tubular epithelial cell in renal fibrogenesis

F. Strutz*, H. Okada, E. G. Neilson

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


Changes in the tubulointerstitial compartment play an important role in the progression of chronic renal disease to endstage renal failure. These changes consist of interstitial inflammation and subsequent fibrosis. The tubular epithelial cell plays a key role in the formation of interstitial inflammation. Stimulated by proteinuria and morphokines in the tubular fluid, the tubular epithelial cell responds by synthesizing chemokines, which, in turn, results in the influx of inflammatory mononuclear cells. Increased tubular expression of adhesion molecules, such as intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1, as well as major histocompatibility complex (MHC) class II antigens, in conjunction with costimulatory molecules, may have additional effects. However, the tubular epithelial cell does not only mediate interstitial inflammation, it also stimulates interstitial fibroblasts via the secretion of cytokines such as platelet-derived growth factor (PDGF), fibroblast growth factor (FGF)-2, and transforming growth factor (TGF)-β. Furthermore, tubular epithelial cells have the capacity to participate in the synthesis of extracellular matrix either directly or indirectly via their transformation into mesenchymal-like fibroblasts. This process of epithelial-mesenchymal transformation (EMT) depends on cytokines such as TGF-β1 and epidermal growth factor (EGF), as well as disruption of the tubular basement membrane (TBM). The contribution of epithelial cell apoptosis to tubular atrophy is actively under investigation.

Original languageEnglish (US)
Pages (from-to)62-74
Number of pages13
JournalClinical and Experimental Nephrology
Issue number2
StatePublished - 2001


  • Autocrine stimulation
  • FGF-2
  • Fibroblast
  • Fibrosis
  • TGF-β1
  • Transdifferentiations

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Physiology (medical)


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