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Therapeutic Potential of Progranulin in Hyperhomocysteinemia-Induced Cardiorenal Dysfunction

Yi Fu1, Yu Sun1, Meng Zhou1

  • 1From the Departments of Pharmacology (Y.F., Y.S., M.Z., X. Wang, Z.W., X. Wei, Y.Z., Z.S., K.L., F.Y.) and Pathogenic Biology (W.T.), Shandong University School of Medicine, Jinan, China.

Hypertension (Dallas, Tex. : 1979)
|November 23, 2016
PubMed

Insights

Progranulin (PGRN) levels decrease in hyperhomocysteinemia (hHcys), worsening cardiorenal injury. PGRN supplementation shows therapeutic potential for hHcys-associated damage.

Area of Science:

  • Cardiovascular Science
  • Nephrology
  • Molecular Biology

Background:

  • Hyperhomocysteinemia (hHcys) is a significant risk factor for cardiovascular and renal diseases.
  • Current therapies for hHcys-induced injury are insufficient, necessitating novel therapeutic targets.
  • Identifying key molecular players in hHcys pathogenesis is crucial for developing new treatment strategies.

Purpose of the Study:

  • To investigate the role of progranulin (PGRN) in hyperhomocysteinemia-induced cardiorenal injury.
  • To elucidate the underlying molecular mechanisms linking PGRN to homocysteine-related damage.
  • To evaluate the therapeutic potential of PGRN in a mouse model of hHcys.

Main Methods:

  • Utilized a mouse model of hyperhomocysteinemia (hHcys).
  • Assessed cardiorenal injury markers, including urinary albumin excretion and renal/myocardial morphology.
  • Investigated PGRN levels and its association with Wnt/β-catenin signaling.
  • Administered recombinant human PGRN to hHcys mice to assess therapeutic effects.

Main Results:

  • Progranulin (PGRN) levels were significantly reduced in the kidney and heart of hHcys mice.
  • PGRN deficiency exacerbated cardiorenal injury in hHcys mice, indicated by increased albuminuria and severe morphological damage.
  • PGRN deficiency led to adverse myocardial remodeling in hHcys mice.
  • PGRN-mediated Wnt/β-catenin signaling was identified as a critical pathway in homocysteine-induced injury.
  • Recombinant human PGRN pretreatment ameliorated cardiorenal injury in hHcys mice.

Conclusions:

  • Progranulin (PGRN) plays a protective role against hyperhomocysteinemia-induced cardiorenal injury.
  • PGRN levels are diminished in hHcys, contributing to disease progression.
  • PGRN, potentially via Wnt/β-catenin signaling, represents a promising therapeutic target for hHcys-associated conditions.

Keywords:
PGRNWnt pathwaycardiac hypertrophyglomerular filtration barrierhomocysteine

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