Key result
Glomerular ACE2 expression was positively correlated with mesangial hypercellularity and significantly increased in 39 pediatric IgA nephropathy patients compared to 14 controls.
Observational (n=53)
Glomerular ACE2 expression is associated with mesangial hypercellularity in early lesions of pediatric IgA nephropathy and is upregulated by pro-inflammatory cytokines like IL-1β.
Supports ACE2 involvement in pediatric IgA mesangial lesions; hypothesis-generating and should not alter current management.
BACKGROUND: Angiotensin-converting enzyme (ACE) 2 is a homolog of ACE and is thought to be a potent counter-regulator against ACE activity. However, the role of ACE2 has not been investigated in pediatric patients with IgA nephropathy (IgAN). This study was performed to examine the relationship between ACE2 expression and the development of pediatric IgAN. METHODS: We performed immunohistochemical analysis of ACE2 and ACE in 39 patients with pediatric IgAN and 14 patients with minor glomerular abnormalities, and elucidated the effects of various cytokines on ACE2 expression in cultured human mesangial cells. RESULTS: ACE2 expression levels in glomeruli and tubules were positively correlated with the mesangial hypercellularity score, while ACE expression levels in glomeruli and tubules are not. Multiple regression analysis showed that the mesangial hypercellularity score correlated with the ACE2 expression level in glomeruli and the urinary protein-creatinine ratio. In IgAN patients not treated with a renin-angiotensin system blocker, ACE2 expression levels in glomeruli were significantly increased compared to patients with minor glomerular abnormalities. IgAN patients treated with a renin-angiotensin system blocker did not show this increase in ACE2 expression. Furthermore, cultured human MC showed increased ACE2 mRNA and protein after treatment with IL-1β, a pro-inflammatory cytokine in IgAN. In fact, glomerular expressions of IL-1β were remarkably increased in patients with IgAN. CONCLUSION: These data indicate that ACE2 expression in glomeruli is associated with mesangial hypercellularity in early lesions of pediatric IgAN.
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Urushihara et al. (2013) conducted an observational in Pediatric IgA nephropathy (n=53). ACE2 expression vs. Minor glomerular abnormalities was evaluated on Correlation between ACE2 expression and mesangial hypercellularity score. Glomerular ACE2 expression was positively correlated with mesangial hypercellularity and significantly increased in 39 pediatric IgA nephropathy patients compared to 14 controls.
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