RT Journal Article
SR Electronic
T1 Mechanisms of Renal Cell Repair and Regeneration after Acute Renal Failure
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 905
OP 912
DO 10.1124/jpet.102.035022
VO 304
IS 3
A1 Nony, Paul A.
A1 Schnellmann, Rick G.
YR 2003
UL http://jpet.aspetjournals.org/content/304/3/905.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics