An Intracellular Matrix Metalloproteinase-2 Isoform Induces Tubular Regulated Necrosis: Implications for Acute Kidney Injury.

An Intracellular Matrix Metalloproteinase-2 Isoform Induces Tubular Regulated Necrosis: Implications for Acute Kidney Injury. Am J Physiol Renal Physiol. 2017 Mar 22;:ajprenal.00461.2016 Authors: Ceron CS, Baligand C, Joshi SK, Wanga S, Cowley PM, Walker JP, Song SH, Mahimkar R, Baker AJ, Raffai RL, Wang ZJ, Lovett DH Abstract Acute kidney injury (AKI) causes severe morbidity, mortality, and chronic kidney disease (CKD). Mortality is particularly marked in the elderly and with pre-existing CKD. Oxidative stress is a common theme in models of AKI induced by ischemia/reperfusion (I/R) injury. We recently characterized an intracellular isoform of matrix metalloproteinase-2 (MMP-2) induced by oxidative stress-mediated activation of an alternate promoter in the first intron of the MMP-2 gene. This generates an N-terminal truncated MMP-2 isoform (NTT-MMP-2) that is intracellular and associated with mitochondria. The NTT-MMP-2 isoform is expressed in kidneys of 14 month old mice and in a mouse model of coronary atherosclerosis and heart failure with CKD. We recently determined that NTT-MMP-2 is induced in human renal transplants with delayed graft function and correlated with tubular cell necrosis. To determine mechanism(s) of action, we generated proximal tubule cell-specific NTT-MMP-2 transgenic mice. While morphologically normal at the light microscopic level at 4 months, ultrastructural studies revealed foci of tubular epithelial cell n...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research