The cyclin-dependent kinase inhibitor p27Kip1 safeguards against inflammatory injury.

The cyclin-dependent kinase inhibitor p27Kip1 controls cell proliferation in response to normal mitogenic stimuli. We show here that p27Kip1 also safeguards against excessive cell proliferation in specific pathophysiologic settings. We used experimental glomerulonephritis as a paradigm for immune mediated inflammation and ureteral obstruction as a model for non-immune mediated inflammation. Renal function was substantially decreased in nephritic p27-/- mice compared with control mice, and this was associated with increased glomerular cell proliferation, apoptosis and matrix protein accumulation. Tubular epithelial cell proliferation and apoptosis was also increased in p27-/- mice following ureteral obstruction. p27Kip1 may have a general role in protecting cells and tissues from inflammatory injury.