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

Journal of Cell Communication and Signaling 06/2010; 4(2):79-90. DOI: 10.1007/s12079-010-0088-9
Source: PubMed


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 E(2) (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 PGE(2) as early as 30 min after onset of shear stress, levels that increased over time. PGE(2) 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 PGE(2) 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 PGE(2) plays an important role in mechanoperception in podocytes.

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Available from: Ram Sharma, Oct 13, 2015
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    • "However, by analogy with other EnC in the vasculature which communicate with underlying smooth muscle cells via nitric oxide (NO), it seems likely such mediators will be released by GEnC to have actions on other glomerular cells. Under physiological conditions, mean glomerular shear stress is estimated at 10–20 dyn/cm 2 (Ballermann et al., 1998), however , there is little data detailing the effects of LSS on GEnC (Eng and Ballermann, 2003) (Bevan et al., 2011), podocytes (Srivastava et al., 2010; Friedrich et al., 2006) or the glomerulus as a whole, and how this impacts on glomerular permeability and cell cross-talk. Here we hypothesise that chronic exposure of GEnC to LSS will modulate expression of KLF2 and its downstream targets and modify communication with podocytes via soluble mediators. "
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