Glomerular angiotensin-converting enzyme 2 in pediatric IgA nephropathy

Area of Science:

• Nephrology
• Immunology
• Molecular Biology

Background:

• Angiotensin-converting enzyme 2 (ACE2) acts as a counter-regulator to ACE, but its role in pediatric IgA nephropathy (IgAN) is unknown.
• Investigating ACE2 expression is crucial for understanding the pathogenesis of pediatric IgAN.

Purpose of the Study:

• To examine the relationship between ACE2 expression and the development of pediatric IgAN.
• To explore the correlation between ACE2, ACE expression, and histological findings in pediatric IgAN patients.

Main Methods:

• Immunohistochemical analysis of ACE2 and ACE in kidney biopsies from pediatric IgAN patients and controls.
• In vitro studies using cultured human mesangial cells to assess cytokine effects on ACE2 expression.
• Correlation analysis between ACE2 expression, histological scores, and clinical parameters like proteinuria and treatment with renin-angiotensin system blockers.

Main Results:

• ACE2 glomerular and tubular expression positively correlated with mesangial hypercellularity scores.
• Mesangial hypercellularity was associated with glomerular ACE2 expression and urinary protein-creatinine ratio.
• Increased glomerular ACE2 expression in IgAN patients not on renin-angiotensin system blockers, particularly those with elevated IL-1β.
• Cultured mesangial cells showed increased ACE2 expression upon IL-1β stimulation.

Conclusions:

• Glomerular ACE2 expression is associated with mesangial hypercellularity in early pediatric IgAN lesions.
• ACE2 upregulation, potentially driven by inflammation (IL-1β), may contribute to early IgAN pathogenesis.
• ACE2's role warrants further investigation in pediatric IgAN management.