Nestin Expression in Adult and Developing Human Kidney

Abstract

S U M M A R Y Nestin is considered a marker of neurogenic and myogenic precursor cells. Its arrangement is regulated by cyclin-dependent kinase 5 (CDK5), which is expressed in murine podocytes. We investigated nestin expression in human adult and fetal kidney as well as CDK5 presence in adult human podocytes. Confocal microscopy demonstrated that adult glomeruli display nestin immunoreactivity in vimentin-expressing cells with the podocyte morphology and not in cells bearing the endothelial marker CD31. Glomerular nestin-positive cells were CDK5 immunoreactive as well. Western blotting of the intermediate filamentenriched cytoskeletal fraction and coimmunoprecipitation of nestin with anti-CDK5 antibodies confirmed these results. Nestin was also detected in developing glomeruli within immature podocytes and a few other cells. Confocal microscopy of experiments conducted with antibodies against nestin and endothelial markers demonstrated that endothelial cells belonging to capillaries invading the lower cleft of S-shaped bodies and the immature glomeruli were nestin immunoreactive. Similar experiments carried out with antibodies raised against nestin and a-smooth muscle actin showed that the first mesangial cells that populate the developing glomeruli expressed nestin. In conclusion, nestin is expressed in the human kidney from the first steps of glomerulogenesis within podocytes, mesangial, and endothelial cells. This expression, restricted to podocytes in mature glomeruli, appears associated with CDK5. (J Histochem Cytochem 55:411-421, 2007)

Nestin Improves Preeclampsia-Like Symptoms by Inhibiting Activity of Cyclin-Dependent Kinase 5

“…Liu et al [17] also showed that the degree of albuminuria in diabetic rats was negatively correlated with the Nestin concentration and positively correlated with the CDK5 level. Roscovitine could reduce the degradation of NestinNestin and ameliorate podocyte injuries [18, 19]. Thus, our findings indicate that the protective role of Nestin on podocytes is mediated by inhibition of the kinase activity of CDK5 when challenged by Ang II.…”

Podocytes Contribute to the Formation of Glomerular Crescents

“…Nestin expression has recently been documented in rat, 13 mouse, 14 and human 11,15 kidney, where expression in mature kidney is limited to podocytes. We have found that nestin ex- pression in normal mature human glomeruli is confined to podocytes and that nestin expression persists in podocytes in every glomerular disease studied.…”

“…We have found that nestin is expressed in human podocytes in normal kidney and all glomerular diseases studied to date. 11 Nestin is an intermediate filament protein that is genetically distinct from other intermediate filaments and was originally identified in neural progenitor cells, 12 but only recently, it has been found that nestin is expressed in rat, 13 mouse, 14 and human 11,15 podocytes. We reasoned that nestin might serve as a robust marker for podocytes, and we have carried out a study of nestin expression in crescentic disease, with the goal of assessing the podocyte contribution to crescents.…”

Nestin Expression Reflects Formation, Revascularization and Reinnervation of New Myofibers in Regenerating Rat Hind Limb Skeletal Muscles

“…Subsequently, due to improving detection methods, nestin expression was described in many other embryonic or fetal tissues, e.g. the presomitic mesoderm [Zimmerman et al, 1994], mesonephric mesenchyme [Fröjdman et al, 1997], developing cardiomyocytes [Kachinski et al, 1995], endothelium in developing blood vessels [Mokrý and Němeček, 1998a;Mokrý et al, 2004], maturing teeth [Terling et al, 1995], lens cells in the developing eye [Mokrý and Němeček, 1998b;Yang et al, 2000], and differentiating podocytes of the kidney [Bertelli et al, 2007], etc. One of the most characteristic features of nestin is its reexpression in situations that reproduce developmental phases.…”