The morphological characteristics and expression of cell cycle regulatory proteins in cellular variants of idiopathic focal segmental glomerulosclerosis.

OBJECTIVE

To investigate the morphological characteristics and expression of cell cycle regulatory proteins in cellular variants of idiopathic focal segmental glomerulosclerosis (FSGS).

METHODS

Seventeen cases of cellular variants of FSGS were studied by light microscopy, immunofluorescence (IF), and electron microscopy (EM). The immunohistochemistry and immunoelectron microscopy for the detection of cyclins (cyclin D1, cyclin E, cyclin A, cyclin B1) and cyclin dependent kinase inhibitors (CKIs, including p21, p27, p57) were performed in these cases.

RESULTS

The hypertrophy and hyperplasia of epithelial cells overlying sclerotic or collapsed glomerular tufts were the prominent characteristics of cellular variants of FSGS; IF showed segmental deposits of IgM; hyperplastic epithelial cells possessed the features of both podocyte and parietal epithelial cells ultrastructurally. Hyperplastic epithelial cells of cellular lesions showed positive staining for cyclin E, cyclin A, cyclin B1 and p21, and negative staining for cyclin D1, p27 and p57.

CONCLUSION

The hyperplastic epithelial cells in cellular variants of FSGS may be derived from damaged podocytes, which mimic the immature podocytes, re-engage the cell cycle to proliferate and form the cellular lesions. The up-regulation of cyclins (cyclin E, cyclin A, cyclin B1) concurrent with the loss of CKIs (p27, p57) contributes to the cell cycle regulation of cellular lesions of FSGS.