TY - JOUR
T1 - Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies
AU - Barisoni, Laura
AU - Mokrzycki, Michele
AU - Sablay, Leonada
AU - Nagata, Michio
AU - Yamase, Harold
AU - Mundel, Peter
N1 - Funding Information:
This work was supported by a grant from the Howard Hughes Medical Research Institute Research Resources for Medical Schools to Peter Mundel. We thank Mr. Jorge Bermudez, Ms. Bruni Hähnel, and Mr. Torsten Heider for expert technical assistance.
PY - 2000
Y1 - 2000
N2 - 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 DI 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. Podoeyte proliferation in CG provides evidence in support of a previously underestimated plasticity of mature podocytes.
AB - 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 DI 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. Podoeyte proliferation in CG provides evidence in support of a previously underestimated plasticity of mature podocytes.
KW - Cyclin-dependent kinase inhibitor
KW - HIV-associated nephropathy
KW - Ki-67
KW - Microcysts
KW - P27 and p57
KW - Tubulointerstitial damage
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U2 - 10.1046/j.1523-1755.2000.00149.x
DO - 10.1046/j.1523-1755.2000.00149.x
M3 - Article
C2 - 10886558
AN - SCOPUS:0033945550
SN - 0085-2538
VL - 58
SP - 137
EP - 143
JO - Kidney international
JF - Kidney international
IS - 1
ER -