CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion

Natasha M. Rogers, Zheng J. Zhang, Jiao Jing Wang, Angus W. Thomson, Jeffrey S. Isenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47-/- mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47-/- renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47-/- mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal.

Original languageEnglish (US)
Pages (from-to)334-347
Number of pages14
JournalKidney international
Issue number2
StatePublished - Aug 1 2016


  • CD47
  • OSKM
  • ischemia-reperfusion injury
  • kidney
  • self-renewal
  • thrombospondin-1

ASJC Scopus subject areas

  • Nephrology


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