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

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Journal of Cell Communication and Signaling Aims and scope

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 (PGE2) 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.

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Acknowledgement

This work was supported in part by The Sam and Helen Kaplan Research Fund in Pediatric Nephrology, Marion Merrell Dow Foundation Clinical Scholar Award and The Norman S. Coplon Extramural Research Grant to TS and AR046798 to MLJ and LFB. We are indebted to Ashley Sherman, MA for statistical assistance.

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None of the authors of this work have financial interests to disclose.

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Authors and Affiliations

  1. Section of Nephrology, Children’s Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO, USA

    Tarak Srivastava & Patricia A. Cudmore

  2. Kidney Institute, University of Kansas Medical Center, Kansas City, KS, USA

    Ellen T. McCarthy

  3. Renal Research Laboratory, Research and Development, Kansas City VA Medical Center, Room F1-130, Building 15, 4801 Linwood Boulevard, Kansas City, MO, 64128, USA

    Ram Sharma

  4. Kidney Disease Center, Medical College of Wisconsin, Milwaukee, WI, USA

    Mukut Sharma

  5. Department of Oral Biology, University of Missouri at Kansas City—School of Dentistry, Kansas, MO, USA

    Mark L. Johnson & Lynda F. Bonewald

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  1. Tarak Srivastava
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Correspondence to Ram Sharma.

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Srivastava, T., McCarthy, E.T., Sharma, R. et al. Prostaglandin E2 is crucial in the response of podocytes to fluid flow shear stress. J. Cell Commun. Signal. 4, 79–90 (2010). https://doi.org/10.1007/s12079-010-0088-9

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