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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Mechanisms of Renal Cell Repair and Regeneration after Acute Renal Failure

Paul A. Nony and Rick G. Schnellmann
Journal of Pharmacology and Experimental Therapeutics March 2003, 304 (3) 905-912; DOI: https://doi.org/10.1124/jpet.102.035022
Paul A. Nony
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Rick G. Schnellmann
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Abstract

In many cases, acute renal failure (ARF) is the result of proximal tubular cell injury and death and can arise in a variety of clinical situations, especially following renal ischemia and drug or toxicant exposure. Although much research has focused on the cellular events leading to ARF, less emphasis has been placed on the mechanisms of renal cell repair and regeneration, although ARF is reversed in over half of those who acquire it. Studies using in vivo and in vitro models have demonstrated the importance of proliferation, migration, and repair of physiological functions of injured renal proximal tubular cells (RPTC) in the reversal of ARF. Growth factors have been shown to produce migration and proliferation of injured RPTC, although the specific mechanisms through which growth factors promote renal regeneration in vivo are unclear. Recently, interactions between integrins and extracellular matrix proteins such as collagen IV were shown to promote the repair of physiological functions in injured RPTC. Specifically, collagen IV synthesis and deposition following cellular injury restored integrin polarity and promoted repair of mitochondrial function and active Na+ transport. Furthermore, exogenous collagen IV, but not collagen I, fibronectin, or laminin, promoted the repair of physiological functions without stimulating proliferation. These findings suggest the importance of establishing and/or maintaining collagen IV-integrin interactions in the stimulation of repair of physiological functions following sublethal cellular injury. Furthermore, the pathway that stimulates repair is distinct from that of proliferation and migration and may be a viable target for pharmacological intervention.

Footnotes

  • DOI: 10.1124/jpet.102.035022

  • Abbreviations:
    ARF
    acute renal failure
    RPTC
    renal proximal tubular cell(s)
    DCVC
    S-(1,2-dichlorovinyl)-l-cysteine
    ECM
    extracellular matrix
    PAI-1
    plasminogen activator inhibitor type I
    EGF
    epidermal growth factor
    TGF-β1
    transforming growth factor β1
    TBHP
    tert-butylhydroperoxide
    AscP
    l-ascorbic acid-2-phosphate
    MMP
    matrix metalloproteinases
    • Received September 7, 2002.
    • Accepted November 22, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 304 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 304, Issue 3
1 Mar 2003
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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Mechanisms of Renal Cell Repair and Regeneration after Acute Renal Failure

Paul A. Nony and Rick G. Schnellmann
Journal of Pharmacology and Experimental Therapeutics March 1, 2003, 304 (3) 905-912; DOI: https://doi.org/10.1124/jpet.102.035022

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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Mechanisms of Renal Cell Repair and Regeneration after Acute Renal Failure

Paul A. Nony and Rick G. Schnellmann
Journal of Pharmacology and Experimental Therapeutics March 1, 2003, 304 (3) 905-912; DOI: https://doi.org/10.1124/jpet.102.035022
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  • Article
    • Abstract
    • RPTC Injury, Repair, and Regeneration
    • In Vitro Models For Studying RPTC Repair
    • Mechanisms of Renal Proximal Tubular Cell Regeneration
    • Repair of Physiological Functions
    • Future Studies in Repair and Regeneration
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