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Am J Physiol Renal Physiol 297: F629-F638, 2009. First published July 8, 2009; doi:10.1152/ajprenal.00213.2009 Free Article
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GEC-targeted HO-1 expression reduces proteinuria in glomerular immune injury

Pu Duann and Elias A. Lianos

Nephrology Division, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Submitted 17 April 2009 ; accepted in final form 2 July 2009

Induction of heme oxygenase (HO)-1 is a key defense mechanism against oxidative stress. Compared with tubules, glomeruli are refractory to HO-1 upregulation in response to injury. This can be a disadvantage as it may be associated with insufficient production of cytoprotective heme-degradation metabolites. We, therefore, explored whether 1) targeted HO-1 expression can be achieved in glomeruli without altering their physiological integrity and 2) this expression reduces proteinuria in immune injury induced by an anti-glomerular basement membrane (GBM) antibody (Ab). We employed a 4.125-kb fragment of a mouse nephrin promoter downstream to which a FLAG-tagged hHO-1 cDNA sequence was inserted and subsequently generated transgenic mice from the FVB/N parental strain. There was a 16-fold higher transgene expression in the kidney than nonspecific background (liver) while the transprotein immunolocalized in glomerular epithelial cells (GEC). There was no change in urinary protein excretion, indicating that GEC-targeted HO-1 expression had no effect on glomerular protein permeability. Urinary protein excretion in transgenic mice with anti-GBM Ab injury (days 3 and 6) was significantly lower compared with wild-type controls. There was no significant change in renal expression levels of profibrotic (TGF-β1) or anti-inflammatory (IL-10) cytokines in transgenic mice with anti-GBM Ab injury. These observations indicate that GEC-targeted HO-1 expression does not alter glomerular physiological integrity and reduces proteinuria in glomerular immune injury.

glomerular epithelial cells; anti-GBM disease; heme oxygenase 1; glomerulonephritis


Address for reprint requests and other correspondence: P. Duann, UMDNJ-Robert Wood Johnson Medical School, Dept. of Medicine/Div. of Nephrology, 1 RWJ Place, PO Box 19, MEB 412, New Brunswick, NJ 08903-0019 (e-mail: duannpu{at}umdnj.edu and lianosea{at}umdnj.edu)






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