Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) and kidney diseases: HCaRG accelerates tubular repair

Hiroyuki Matsuda, Pavel Hamet, Johanne Tremblay

Research output: Contribution to journalReview articlepeer-review

8 Citations (Scopus)

Abstract

Hypertension is a risk factor for renal impairment. While treatment of hypertension provides significant renal protection, there is still an unmet need requiring further exploration of additional pathogenetic mechanisms. We have found that the hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is involved in renal repair. HCaRG is a small intracellular protein of 225 amino acids and its gene expression is negatively regulated by extracellular calcium concentrations. HCaRG is mostly expressed in the kidneys, with higher levels found in the spontaneously hypertensive rat than in normotensive rats. In an acute kidney injury model, HCaRG expression decreases immediately after injury but increases above baseline during the repair phase. In cell cultures, HCaRG has been shown to facilitate differentiation and to inhibit cell proliferation via p21 transactivation through the p53-independent signaling pathway. Induction of p21 independently of p53 is also observed in transgenic mice overexpressing HCaRG during the repair phase after ischemia/reperfusion injury, resulting in their improved renal function and survival with rapid re-differentiation of proximal tubular epithelial cells. In addition, transgenic mice recover rapidly from the inflammatory burst most likely as a result of maintenance of the tubular epithelial barrier. Recent studies indicate that facilitating re-differentiation and cell cycle regulation in injured renal proximal tubules might be important functions of HCaRG. We have proposed that HCaRG is a component of differential genetic susceptibility to renal impairment in response to hypertension.

Original languageEnglish
Pages (from-to)351-360
Number of pages10
JournalJournal of Nephrology
Volume27
Issue number4
DOIs
Publication statusPublished - Aug 2014
Externally publishedYes

Keywords

  • Acute kidney injury
  • Copper metabolism MURR1 domain-containing proteins
  • Hypertension-related calcium-regulated gene
  • Re-differentiation
  • Renal repair
  • p21

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