Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies

Laura Barisoni, Michele Mokrzycki, Leonada Sablay, Michio Nagata, Harold Yamase, Peter Mundel

Research output: Contribution to journalArticlepeer-review

175 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)137-143
Number of pages7
JournalKidney international
Volume58
Issue number1
DOIs
StatePublished - 2000

Keywords

  • Cyclin-dependent kinase inhibitor
  • HIV-associated nephropathy
  • Ki-67
  • Microcysts
  • P27 and p57
  • Tubulointerstitial damage

ASJC Scopus subject areas

  • Nephrology

Fingerprint

Dive into the research topics of 'Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies'. Together they form a unique fingerprint.

Cite this