Glomerular inflammation induces resistance to tubular injury in the rat. A novel form of acquired, heme oxygenase-dependent resistance to renal injury.

Abstract

Considerable attention is directed to a surprising biologic phenomenon wherein tissues exposed to one insult acquire resistance to another. We identify a novel example of acquired resistance to acute renal failure and a mechanism that contributes to such resistance. Nephrotoxic serum, administered to rats 24 h before the induction of glycerol-induced acute renal failure, reduces functional and structural injury that occurs in this model. Since heme oxygenase, the ratelimiting enzyme in heme degradation, protects against heme protein-induced renal injury, we questioned whether induction of heme oxygenase underlies the protection afforded by nephrotoxic serum. Kidney heme oxygenase (HO-1) mRNA was induced 6 h after nephrotoxic serum and renal tubules were identified as the site of expression of heme oxygenase protein.

Gene Transfer-Induced Local Heme Oxygenase-1 Overexpression Protects Rat Kidney Transplants From Ischemia/Reperfusion Injury

“…In analogy with heat shock regulation, HO-1 overexpression in kidneys represents a critical endogenous adaptive mechanism protecting cells from stress following radiation (31), heat shock (32), inflammation (33,34), and ischemia (35). Indeed, HO-1 overexpression after gene transfer in this study prevented or significantly decreased renal injury in a stringent and clinically relevant model of 24-h cold ischemia followed by syngeneic transplantation.…”

Heme Oxygenase-1 Deficiency Promotes Epithelial-Mesenchymal Transition and Renal Fibrosis

“…2 Whereas HO-1 downregulates the inflammatory response in both renal and nonrenal tissues, 18,38 repeated exposure of HO-1 Ϫ/Ϫ mice to heme proteins leads to intense interstitial cellular inflammation with significant increase in the expression of MCP-1. 39 Proximal tubular cells overexpressing HO-1 had lower MCP-1 mRNA and protein expression in response to albumin, compared with similarly treated control cells.…”

Accommodation: Preventing Injury in Transplantation and Disease

“…Vogt et al (34) showed that exposure to nephrotoxic serum protects rats from subsequent glycerol-induced acute renal failure also thought to be due to heme oxygenase-1 expression. The protective mechanisms described in these models of renal injury were extended to accommodation by Bach et al (35), who found that accommodated grafts also express heme oxygenase-1 in addition to the antiapoptotic genes A20, Bcl-2, and Bcl-x L , whereas grafts undergoing acute vascular rejection express the proapoptotic genes Bad and Bax.…”