Expression and regulation of αB-crystallin in the kidney in vivo and in vitro

Abstract

alphaB-crystallin, a major component of the mammalian eye lens, is a small heat shock protein and molecular chaperone that is also abundant in the mammalian kidney. The present study aimed to characterize more closely the intrarenal expression and regulation of alphaB-crystallin in vivo and in vitro. In normal rat kidney, the expression of alphaB-crystallin mRNA and protein were both close to the detection limit in cortex, but increased steeply from the outer to the inner medulla where alphaB-crystallin constitutes approximately 2% of total tissue protein. Immunohistochemistry disclosed papillary collecting duct cells and thin limbs as the major sites for intrapapillary alphaB-crystallin immunoreactivity. In rats subjected to sucrose diuresis for 3 days, alphaB-crystallin mRNA expression was reduced by 27 and 46% in outer and inner medulla, respectively. In agreement with the results obtained in vivo, in Madine-Darby canine kidney cells, alphaB-crystallin mRNA and protein were induced significantly by elevating the medium osmolality to 500 mosm/kg H(2)O by the addition of NaCl and raffinose, and also by urea. The NaCl-induced increase in alphaB-crystallin expression was concentration-dependently blunted by SP600125, a specific JNK inhibitor. Overexpression of alphaB-crystallin in 293 cells resulted in increased tolerance to acute osmotic stress. These results indicate that alphaB-crystallin may be regulated by papillary interstitial tonicity in a JNK-dependent process. Moreover, the high abundance of alphaB-crystallin in the renal medulla may be important for cell survival in an environment characterized by extreme interstitial solute concentrations as present during antidiuresis.