Charles Thodeti - Academia.edu (original) (raw)
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Papers by Charles Thodeti
Journal of Cellular Physiology, 2012
Cilia are mechanosensing organelles that communicate extracellular signals into intracellular res... more Cilia are mechanosensing organelles that communicate extracellular signals into intracellular responses. Altered functions of primary cilia play a key role in the development of various diseases including polycystic kidney disease. Here, we show that endothelial cells from the oak ridge polycystic kidney (Tg737 orpk/orpk ) mouse, with impaired cilia assembly, exhibit a reduction in the actin stress fibers and focal adhesions compared to wild-type (WT). In contrast, endothelial cells from polycystin-1 deficient mice (pkd1 null/null ), with impaired cilia function, display robust stress fibers, and focal adhesion assembly. We found that the Tg737 orpk/orpk cells exhibit impaired directional migration and endothelial cell monolayer permeability compared to the WT and pkd1 null/null cells. Finally, we found that the expression of heat shock protein 27 (hsp27) and the phosphorylation of focal adhesion kinase (FAK) are downregulated in the Tg737 orpk/orpk cells and overexpression of hsp27 restored both FAK phosphorylation and cell migration. Taken together, these results demonstrate that disruption of the primary cilia structure or function compromises the endothelium through the suppression of hsp27 dependent actin organization and focal adhesion formation, which may contribute to the vascular dysfunction in ciliopathies.
Journal of Cellular Physiology, 2012
Cilia are mechanosensing organelles that communicate extracellular signals into intracellular res... more Cilia are mechanosensing organelles that communicate extracellular signals into intracellular responses. Altered functions of primary cilia play a key role in the development of various diseases including polycystic kidney disease. Here, we show that endothelial cells from the oak ridge polycystic kidney (Tg737 orpk/orpk ) mouse, with impaired cilia assembly, exhibit a reduction in the actin stress fibers and focal adhesions compared to wild-type (WT). In contrast, endothelial cells from polycystin-1 deficient mice (pkd1 null/null ), with impaired cilia function, display robust stress fibers, and focal adhesion assembly. We found that the Tg737 orpk/orpk cells exhibit impaired directional migration and endothelial cell monolayer permeability compared to the WT and pkd1 null/null cells. Finally, we found that the expression of heat shock protein 27 (hsp27) and the phosphorylation of focal adhesion kinase (FAK) are downregulated in the Tg737 orpk/orpk cells and overexpression of hsp27 restored both FAK phosphorylation and cell migration. Taken together, these results demonstrate that disruption of the primary cilia structure or function compromises the endothelium through the suppression of hsp27 dependent actin organization and focal adhesion formation, which may contribute to the vascular dysfunction in ciliopathies.