Aim
Mutations of the inverted formin 2 gene (INF2), which encodes a member of the formin family, cause autosomal dominant focal segmental glomerulosclerosis (FSGS) and Charcot-Marie-Tooth (CMT) disease-associated FSGS. However, their role in idiopathic FSGS remains unclear. This study investigated INF2 localization in the normal adult kidney and its expression in children with idiopathic nephrotic syndrome.
Conclusion
We propose that examination of INF2 expression may help to differentiate MCD from FSGS and evaluate the clinical severity of SRNS in children.
Methods
We generated a rabbit polyclonal antibody against the conjugated peptide from human INF2 and studied the glomerular expression of INF2 and synaptopodin using normal human adult kidney tissues and tissues from children with glomerular diseases such as minimal change disease (MCD), FSGS, IgA nephropathy (IgAN), non-IgA mesangial proliferative glomerulonephritis (non-IgAN), and Henoch-Schönlein purpura nephritis (HSPN).
Results
The anti-INF2 antibody detected an approximately 140-kD fragment isolated from adult mature glomeruli by western blotting. Immunohistochemically, INF2 was detected in podocytes and renal arteries. Among 56 patients, INF2 in glomeruli was expressed at a similar level in patients with MCD, IgAN, non-IgAN, or HSPN and controls. In FSGS patients, INF2 expression in glomeruli was either decreased or absent. There was a relationship between decreased INF2 expression and the clinical severity of steroid resistant nephrotic syndrome (SRNS).