Prostaglandin E2 is crucial in the response of podocytes to fluid flow shear stress

Tarak Srivastava, Ellen T. McCarthy, Ram Sharma, Patricia A. Cudmore, Mukut Sharma, Mark L. Johnson, Lynda F. Bonewald

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Podocytes play a key role in maintaining and modulating the filtration barrier of the glomerulus. Because of their location, podocytes are exposed to mechanical strain in the form of fluid flow shear stress (FFSS). Several human diseases are characterized by glomerular hyperfiltration, such as diabetes mellitus and hypertension. The response of podocytes to FFSS at physiological or pathological levels is not known. We exposed cultured podocytes to FFSS, and studied changes in actin cytoskeleton, prostaglandin E2 (PGE 2) production and expression of cyclooxygenase-1 and-2 (COX-1, COX-2). FFSS caused a reduction in transversal F-actin stress filaments and the appearance of cortical actin network in the early recovery period. Cells exhibited a pattern similar to control state by 24 h following FFSS without significant loss of podocytes or apoptosis. FFSS caused increased levels of PGE2 as early as 30 min after onset of shear stress, levels that increased over time. PGE2 production by podocytes at post- 2 h and post-24 h was also significantly increased compared to control cells (p<0.039 and 0.012, respectively). Intracellular PGE2 synthesis and expression of COX-2 was increased at post-2 h following FFSS. The expression of COX-1 mRNA was unchanged. We conclude that podocytes are sensitive and responsive to FFSS, exhibiting morphological and physiological changes. We believe that PGE2 plays an important role in mechanoperception in podocytes.

Original languageEnglish (US)
Pages (from-to)79-90
Number of pages12
JournalJournal of Cell Communication and Signaling
Volume4
Issue number2
DOIs
StatePublished - Jun 1 2010

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Keywords

  • Actin
  • Cyclooxygenase
  • Mechanical strain
  • Prostaglandin E
  • Shear stress

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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