[HTML][HTML] Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies
Kidney international, 2000•Elsevier
Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies. Background
Mature podocytes are growth-arrested because of the expression of cyclin-dependent
kinase inhibitors. Under pathological conditions, podocytes may undergo mitosis, but not
cell division. Exceptions to this rule are collapsing glomerulopathies (CGs), including HIV-
associated nephropathy (HIVAN) and idiopathic CG, where podocytes undergo a
dysregulation of their differentiated phenotype and proliferate. Methods To shed light on the …
Mature podocytes are growth-arrested because of the expression of cyclin-dependent
kinase inhibitors. Under pathological conditions, podocytes may undergo mitosis, but not
cell division. Exceptions to this rule are collapsing glomerulopathies (CGs), including HIV-
associated nephropathy (HIVAN) and idiopathic CG, where podocytes undergo a
dysregulation of their differentiated phenotype and proliferate. Methods To shed light on the …
Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies.
Background
Mature podocytes are growth-arrested because of the expression of cyclin-dependent kinase inhibitors. Under pathological conditions, podocytes may undergo mitosis, but not cell division. Exceptions to this rule are collapsing glomerulopathies (CGs), including HIV-associated nephropathy (HIVAN) and idiopathic CG, where podocytes undergo a dysregulation of their differentiated phenotype and proliferate.
Methods
To shed light on the mechanism underlying podocyte proliferation in CG, we analyzed the expression of the proliferation marker Ki-67, cyclins (A, D1), cyclin-dependent kinase inhibitors (p27, p57), and podocyte differentiation marker synaptopodin in eight cases of HIVAN and two cases of idiopathic CG. Normal fetal and adult kidneys served as controls.
Results
Both HIVAN and idiopathic CG showed a marked reduction in the expression of p27, p57, and cyclin D1 (absent in 69, 62, and 80% of all glomeruli, respectively). Cyclin A and Ki-67 were expressed in 11 and 29% of all glomeruli. Moreover, there was partial loss of synaptopodin and cyclin D1 expression in nonaffected glomeruli.
Conclusions
The loss of p27 and p57 leading to expression of cyclin A may account for the activation of podocyte proliferation in CG. Furthermore, the loss of cyclin D1 from histologically normal glomeruli suggests a possible role of cyclin D1 in mediating the dysregulation of the podocyte cell cycle in CG. These novel findings offer insight into the molecular regulation of mature podocyte differentiation. Podocyte proliferation in CG provides evidence in support of a previously underestimated plasticity of mature podocytes.
Elsevier