Enhanced tubular epithelial CD44 expression in MRL-lpr lupus nephritis

Kidney Int. 1996 Jul;50(1):156-63. doi: 10.1038/ki.1996.298.


The cell surface glycoprotein CD44 is expressed by cells of hematopoietic origin and constitutes a receptor for hyaluronic acid and matrix proteins. Because CD44 could play a role in recruiting inflammatory cells to sites of immune injury, we examined the renal CD44 expression in normal and in autoimmune MRL-lpr mice by immunohistochemistry and at a molecular level. In normal kidneys, immunoperoxidase staining for CD44 is restricted to interstitial cells and certain urothelial cells. In nephritic MRL-lpr, CD44 expression is prominent in perivascular inflammatory infiltrates and in glomerular crescents. Interestingly, CD44 is also focally expressed by cortical tubular epithelial cells (TEC) in nephritic MRL-lpr kidneys but not in normal kidneys. Reverse transcription-polymerase chain reaction (RT-PCR) as well as Northern blotting demonstrate that CD44 kidney mRNA levels are increased in nephritic MRL-lpr mice compared with normal mice. To further characterize the tubular CD44 expression, we examined cultured TEC (primary cultures and SV40-transformed TEC lines C1 and MCT). TEC constitutively express abundant cell surface CD44 that is modestly up-regulated in response to 18 hours stimulation with TNF-alpha (100 ng/ml), IFN-gamma (100 U/ml) and IL-1 (100 ng/ml). Northern analysis of TEC mRNA reveals a constitutive CD44 mRNA transcript at 3 kb. Stimulation with IFN-gamma or TNF-alpha for six hours markedly up-regulates CD44 mRNA expression in these cells. We conclude that mononuclear infiltration with CD44 positive cells and cytokine-induced up-regulation of CD44 by renal TEC is a prominent feature of MRL-lpr lupus nephritis. The contribution of CD44 induction on TEC to the pathogenesis of the autoimmune nephritic process in MRL-lpr remains to be determined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Epithelium / chemistry
  • Hyaluronan Receptors / analysis*
  • Interferon-gamma / pharmacology
  • Kidney Tubules / chemistry*
  • Lupus Nephritis / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr
  • Tumor Necrosis Factor-alpha / pharmacology


  • Hyaluronan Receptors
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma