Cell Cycle Regulatory Proteins in Glomerular Disease

The growth response of resident glomerular cells is determined by the underlying disease. Thus glomerular cells can proliferate, fail to proliferate, hypertrophy or apoptose. Cell growth is controlled by cell cycle regulatory proteins, and cell proliferation requires that cyclin-dependent kinases (CDK) be activated by partner cyclins. Inhibiting CDK2 reduces mesangial cell proliferation. Mesangial cell proliferation also requires that levels of specific cyclin kinase inhibitors (CKI) decrease. In contrast, the visceral glomerular epithelial cells' inability to proliferate may be due to increased levels of CKI. Moreover it is becoming increasingly clear that mesangial cell hypertrophy in diabetes requires increased CKI expression. Finally, apoptosis, which is often linked to proliferation, may also be due to the increased activity of CDK2. Thus, identifying specific cell cycle regulatory proteins following injury may provide future targets for therapy in glomerular disease.