The renal connexome and possible roles of connexins in kidney diseases

Gabriele Sala, Salvatore Badalamenti, Claudio Ponticelli

Research output: Contribution to journalArticle

Abstract

Connexins are membrane-spanning proteins that allow for the formation of cell-to-cell channels and cell-to-extracellular space hemichannels. Many connexin subtypes are expressed in kidney cells. Some mutations in connexin genes have been linked to various human pathologies, including cardiovascular, neurodegenerative, lung, and skin diseases, but the exact role of connexins in kidney disease remains unclear. Some hypotheses about a connection between genetic mutations, endoplasmic reticulum (ER) stress, and the unfolded protein response (UPR) in kidney pathology have been explored. The potential relationship of kidney disease to abnormal production of connexin proteins, mutations in their genes together with ER stress, or the UPR is still a matter of debate. In this scenario, it is tantalizing to speculate about a possible role of connexins in the setting of kidney pathologies that are thought to be caused by a deregulated podocyte protein expression, the so-called podocytopathies. In this article, we give examples of the roles of connexins in kidney (patho)physiology and propose avenues for further research concerning connexins, ER stress, and UPR in podocytopathies that may ultimately help refine drug treatment.

Original languageEnglish
Pages (from-to)677-687
Number of pages11
JournalAmerican Journal of Kidney Diseases
Volume67
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

Keywords

  • Connexins
  • cytoskeleton
  • drug research
  • endoplasmic reticulum (ER)
  • ER stress
  • gap junctions
  • kidney pathology
  • mutation
  • nephrotic syndrome
  • podocytes
  • proteinuria
  • review
  • slit diaphragm
  • steroid-resistant
  • unfolded protein response (UPR)

ASJC Scopus subject areas

  • Nephrology

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