Developmental expression of HSP-72 and ischemic tolerance of the immature kidney

Abstract.

The resistance of the immature kidney to ischemic injury is well documented, but the mechanisms involved in this tolerance have been elusive. Previous studies have demonstrated that tubules obtained from immature rats exhibit a bigger stress response than mature tubules. Consequently, we evaluated the developmental expression of HSP-72 in the postnatal kidney and determined whether or not that pattern of expression was correlated with the previously known tolerance of the immature kidney to injury. A distinct pattern of HSP-72 expression with a peak abundance at postnatal day 10 (P10), with a subsequent decline toward values seen in mature rats, was found. Moreover, this stress protein is located predominantly in tubular segments, the site of ischemic injury. To determine if this constitutive, non-induced expression of HSP-72 in the immature rat could be protective of cellular integrity and renal function, both immature (P10) and mature (8 weeks) rats were subjected to 45 min of bilateral renal artery ischemia. The postischemic induction of HSP-72 in the P10 animals was robust and the peak expression 2 h after ischemia was even greater than that detected in mature animals. Thus, the constitutive enhanced expression of HSP-72 did not prohibit or mute the inducible response of this stress protein in the immature animals. Immature animals, when compared with mature rats, also experienced cytoprotection, demonstrated by decreased detachment of Na-/K-ATPase from the cytoskeleton and substantial protection of renal function determined by serum creatinine level. These findings suggest that the developmental expression of heat shock proteins may play a critical and fundamental role in the well-observed tolerance of immature tubules to ischemic or anoxic injury.