Regulation of the mesangial cell myofibroblast phenotype by actin polymerization

Patel, Keyur; Harding, Pamela; Haney, Lisa B.; Glass, William F.

doi:10.1002/jcp.10267

Cited by 35 publications

(20 citation statements)

References 86 publications

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“…There is evidence that treatment of HeLa cells with adenovirus infection or trypsin/EDTA, which lead to modifications in cell shape (rounding up) and motility, are not coupled to an alteration in the actin content (Blikstad and Carlsson, 1982). Cytoskeleton is a target for marine toxins known actin-depolymerizing toxin) causes a marked loss of Factin, but has no effect on cell morphology (Patel et al, 2003). In agreement with this, we found that the morphology of intestinal cells did not seem to be affected by any of the toxins that induced a notable effect on actin levels.…”

Section: Discussionmentioning

confidence: 99%

Actin cytoskeleton of rabbit intestinal cells is a target for potent marine phycotoxins

Ares

Louzao

Vieytes

et al. 2005

Journal of Experimental Biology

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Biotoxins produced by harmful marine microalgae (phycotoxins) can be accumulated into seafood, representing a great risk for public health. Some of these phycotoxins are responsible for a variety of gastrointestinal disturbances; however, the relationship between their mechanism of action and toxicity in intestinal cells is still unknown. The actin cytoskeleton is an important and highly complicated structure in intestinal cells, and on that basis our aim has been to investigate the effect of representative phycotoxins on the enterocyte cytoskeleton. We have quantified for the first time the loss of enterocyte microfilament network induced by each toxin and recorded fluorescence images using a laser-scanning cytometer and confocal microscopy. Our data show that pectenotoxin-6, maitotoxin, palytoxin and ostreocin-D cause a significant reduction in the actin cytoskeleton. In addition, we found that the potency of maitotoxin, palytoxin and ostreocin-D to damage filamentous actin is related to Ca 2+ influx in enterocytes. Those results identify the cytoskeleton as an early target for the toxic effect of those toxins.

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Section: Discussionmentioning

confidence: 99%

Actin cytoskeleton of rabbit intestinal cells is a target for potent marine phycotoxins

Ares

Louzao

Vieytes

et al. 2005

Journal of Experimental Biology

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“…Mack et al (42) reported that smooth muscle differentiation marker gene expression is regulated by Rhokinase-mediated actin polymerization and that Rho-kinase inhibition blocks the synthesis of the ␣-SMA isoform. It also was shown that Rho-kinase regulates ␣-SMA promoter activity in glomerular mesangial cells (43) and induces mesenchymal transdifferentiation of proximal tubular cells (44). Further in vitro studies demonstrated that TGF-␤ 1 induces mesenchymal transdifferentiation through RhoA-dependent pathway (45).…”

Section: Figure 2 Photomicrographs Of Glomeruli (A Through E) Glomementioning

confidence: 95%

“…Enhanced expression of ␣-SMA is a marker of interstitial phenotypic changes in renal fibrosis, and these activated interstitial cells are known as myofibroblasts (36,38). It is interesting that it also has been revealed that the Rho-kinase signaling pathway plays a key role in the regulation of myofibroblastic transformation (22,(42)(43)(44)(45). In mouse kidneys with unilateral ureteral obstruction, treatment with a Rho-kinase inhibitor attenuated renal interstitial ␣-SMA expression and fibrosis (22).…”

Section: Figure 2 Photomicrographs Of Glomeruli (A Through E) Glomementioning

confidence: 99%

Involvements of Rho-Kinase and TGF-β Pathways in Aldosterone-Induced Renal Injury

Sun

Kohno

Guo

et al. 2006

Journal of the American Society of Nephrology

110

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Recent studies have suggested a role for aldosterone in the pathogenesis of renal injury. This study investigated the potential contributions of Rho-kinase and TGF-␤ pathways to aldosterone-induced renal injury. Rats were uninephrectomized and then treated for 5 wk with 1% NaCl in a drinking solution and one of the following: Vehicle (2% ethanol, subcutaneously; n ‫؍‬ 9); aldosterone (0.75 g/h, subcutaneously; n ‫؍‬ 9); or aldosterone ؉ fasudil, a specific Rho-kinase inhibitor (10 mg/kg per d, subcutaneously; n ‫؍‬ 8). Phosphorylation of myosin phosphate target subunit-1 (MYPT1) and Smad2/3 in renal cortical tissue was measured by Western blotting with anti-phospho MYPT1 and Smad2/3 antibodies, respectively. Rats that received aldosterone infusion exhibited hypertension and severe renal injury characterized by proteinuria, glomerular sclerosis, and tubulointerstitial fibrosis with increases in ␣-smooth muscle actin staining and numbers of monocytes/macrophages in the interstitium. Renal cortical mRNA levels of types I and III collagen, TGF-␤, connective tissue growth factor, and monocyte chemoattractant protein-1 as well as Smad2/3 phosphorylation were significantly increased in rats that received aldosterone infusion. All of these changes were associated with an increase in renal tissue MYPT1 phosphorylation. Treatment with fasudil did not alter BP but significantly ameliorated proteinuria and renal injury in rats that received aldosterone infusion. Severe glomerular injury and interstitial fibrosis were observed in rats that were treated long term with aldosterone/ salt (3,4). Moreover, exogenous infusion of aldosterone reversed the renoprotective effects of angiotensin II blockade in remnant kidney hypertensive rats (5). In stroke-prone spontaneously hypertensive rats (6); Dahl salt-sensitive hypertensive rats (7); and rats that were treated with angiotensin II and a nitric oxide synthase inhibitor (8), cyclosporine A (9), or radiation (10), treatment with mineralocorticoid receptor (MR) antagonists had no effect on systemic BP (SBP) but significantly ameliorated renal injury. In patients with chronic renal failure (11) and early diabetic nephropathy (12), the addition of MR antagonists to angiotensin-converting enzyme (ACE) inhibitors had no hemodynamic effects but markedly reduced proteinuria. Further studies also showed that monotherapy with MR antagonists was more effective than ACE inhibitors in reducing proteinuria in hypertensive patients (13,14). We recently found that aldosterone stimulates reactive oxygen species production (15) and induces cell proliferation (16) or deformation (16) in cultured glomerular mesangial cells. In addition, aldosterone stimulated collagen synthesis in cultured renal fibroblasts (17). Collectively, these data suggest that aldosterone has deleterious effects on the kidney that cannot be explained simply by BP changes. However, the precise mechanisms that are responsible for aldosterone-induced renal injury remain undetermined.Rho-kinase, an effector of the small G protein ...

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“…Furthermore, similar to renal tubular epithelial cells, mesangial cells also employ transdifferentiation into myofibroblasts in various glomerular diseases (19). This transdifferentiation is characterized by the activation of smooth muscle α-actin expression, and Rho-kinase inhibitors, Y-27632 and HA-1077, block this process in cultured renal mesangial cells (20). Finally, in mesangial cells, mechanical stress, which is considered to cause glomerular hypertension and glomerulosclerosis, enhances mitogen-activated protein kinase (MAP kinase) activity, stress fiber formation, and cellular proliferation (21).…”

Section: Role Of Rho / Rho-kinase In the Kidneymentioning

confidence: 99%

Molecular Mechanisms and Therapeutic Strategies of Chronic Renal Injury: Role of Rho-Kinase in the Development of Renal Injury

et al. 2006

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Abstract. Rho/ Rho-kinase plays an important role not only in the vasoconstrictor mechanism but also in cellular morphology, motility, adhesion, and proliferation. This pathway also serves to modulate the structure and function of various kidney cells including tubular epithelial cells, mesangial cells, and podocytes. The inhibition of the Rho / Rho-kinase pathway elicits marked increases in renal blood flow in vivo and dilates both afferent and efferent arterioles preconstricted by angiotensin II in vitro. In renal injury, intrarenal angiotensin II is reported to be activated, which subsequently would upregulate the Rho-kinase pathway. A selective Rho-kinase inhibitor, fasudil, has recently been shown to improve renal damage resulting from hypertensive glomerulosclerosis, unilateral ureteral obstruction (for interstitial renal fibrosis) and subtotal nephrectomy. Of interest, fasudil upregulated the expression of p27 kip1 , a cyclin-dependent kinase inhibitor, and increased the p27 kip1 immuno-positive cells in both glomeruli and tubulointerstitium with the use of immunohistochemistry. Collectively, the Rho-kinase pathway is involved in the pathogenesis of renal injury. Clinical application of this type of therapy however awaits further investigations.

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Regulation of the mesangial cell myofibroblast phenotype by actin polymerization

Cited by 35 publications

References 86 publications

Actin cytoskeleton of rabbit intestinal cells is a target for potent marine phycotoxins

Actin cytoskeleton of rabbit intestinal cells is a target for potent marine phycotoxins

Involvements of Rho-Kinase and TGF-β Pathways in Aldosterone-Induced Renal Injury

Molecular Mechanisms and Therapeutic Strategies of Chronic Renal Injury: Role of Rho-Kinase in the Development of Renal Injury

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