Discrepancy between Intrarenal Messenger RNA and Protein Expression of ACE and ACE2 in Human Diabetic Nephropathy

Abstract

Background: The intrarenal angiotensin-converting enzyme (ACE) and type 2 ACE (ACE2) play important roles in the pathogenesis of diabetic nephropathy, but human data are limited. We studied glomerular and tubulointerstitial mRNA and the protein expression of ACE and ACE2 in patients with diabetic nephropathy. Methods: We studied renal biopsy specimens of 22 patients with diabetic nephropathy and 11 transplant donors as normal controls. Intrarenal mRNA expression of ACE and ACE2 was measured by laser microdissection and real-time quantitative polymerase chain reaction; expression at the protein level was determined by immunostaining. Results: Glomerular and tubulointerstitial mRNA expression levels of ACE and ACE2 were significantly higher in patients with diabetic nephropathy than in normal controls (p < 0.001 for all comparisons). Glomerular ACE and ACE2 protein levels of patients with diabetic nephropathy were significantly higher than those of kidney donors (4.90 ± 2.55% vs. 2.64 ± 0.98%, p = 0.022, and 7.40 ± 3.36% vs. 4.37 ± 2.36%, p = 0.017, respectively). The tubulointerstitial ACE at the protein level, however, was similar between diabetic patients and controls (8.76 ± 4.18% vs. 10.44 ± 6.61%, p = 0.453), and the tubulointerstitial ACE2 at the protein level was significantly lower in diabetic nephropathy (16.48 ± 7.68% vs. 23.23 ± 7.65%, p = 0.025). Conclusion: The mRNA expression of ACE and ACE2 increased in both the glomerular and tubulointerstitial area of diabetic nephropathy. However, the tubulointerstitial ACE expression at the protein level remained unchanged, while that of ACE2 actually decreased. Our results suggest a posttranscriptional modulation of tubulointerstitial ACE and ACE2 expression. Experimental data of intrarenal mRNA expression of ACE and ACE2 should be interpreted with caution.