Alteration of Cellular Function in Rat Mesangial Cells in Response to Mechanical Stretch Relaxation

Yasuda, Takashi; Akai, Youichi; Kondo, Satoshi; Becker, Bryan N.; Homma, Teiichi; Owada, Shigeru; Ishida, Masaharu; Harris, Raymond C.

doi:10.1159/000425097

Cited by 11 publications

(4 citation statements)

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“…Concordantly, c-fos induction in this setting was also inhibited by 17␤-estradiol. We and others have shown that MAPK-AP-1 signaling is a critical inducer of proliferation in stretched MC (9,12,35). The ability of 17␤-estradiol to inhibit this signaling pathway was not via up-regulation of ER␣, since incubation of MC with 10 Ϫ8 17␤-estradiol for 24 h did not affect ER␣ expression by Western blot.…”

Section: Discussionmentioning

confidence: 80%

17β-Estradiol Modulates Mechanical Strain-induced MAPK Activation in Mesangial Cells

Krepinsky¹,

Ingram²,

James³

et al. 2002

Journal of Biological Chemistry

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Gender is an important determinant of clinical outcome across a broad spectrum of kidney diseases, but the mechanism(s) responsible for the protective effect of female gender have not been fully elucidated. Remnant kidney glomerular injury is limited in female rats compared with male rats despite similar elevations in glomerular capillary pressure. In vitro, mechanical strain leads to the activation of p44/42 mitogen-activated kinase (p44/42 MAPK) and Jun N-terminal kinase/stressactivated protein kinase (SAPK) in glomerular mesangial cells (MC). Accordingly, we studied the effect of 17␤-estradiol on mechanical strain-induced signal transduction in MC. Exposure of MC to mechanical strain increased p44/42 MAPK activation (3-fold) and SAPK activation (2.5-fold), and kinase activation was inhibited by pretreatment with 17␤-estradiol (10 ؊8 to 10 ؊11 M) for 24 h in a dose-dependent manner. Mechanical strain-induced nuclear translocation of p44/42 MAPK and SAPK and nuclear protein binding to AP-1 were also attenuated by 17␤-estradiol. The inhibitory effects of 17␤-estradiol were not reproduced by the cellimpermeable estrogen, BSA/17␤-estradiol, nor did preincubation with 17␤-estradiol lead to actin cytoskeleton disassembly or impaired stress fiber formation. However, 17␤-estradiol did increase base-line levels of the dual specificity phosphatase MKP-1. The inhibitory effects of 17␤-estradiol on p44/42 MAPK activation and SAPK activation, translocation, and AP-1 binding were all abrogated by the estrogen receptor antagonist, ICI-182,780. We conclude that attenuation of mechanical strain-induced MAPK activation by 17␤-estradiol is dependent on intracellular estrogen receptor. The attenuation of stretch-induced kinase activation may be due, at least in part, to an effect of 17␤-estradiol on MKP-1 expression. Together, these findings add insight into the protective effect of gender on renal disease progression.

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Section: Discussionmentioning

confidence: 80%

17β-Estradiol Modulates Mechanical Strain-induced MAPK Activation in Mesangial Cells

Krepinsky¹,

Ingram²,

James³

et al. 2002

Journal of Biological Chemistry

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“…In this regard, it is notable that Hall et al (13) showed that vasopressin escape did not occur in dogs in which renal perfusion pressure was servo-controlled, suggesting that vasopressin escape is mediated by increased renal perfusion. Increased renal perfusion pressure due to ECF volume expansion would be expected to cause stretching of renal vascular endothelial cells, as well as glomerular mesangial cells (1,32). It has been reported that shear stress stimulates the production of NO and PG through stretchactivated ion channels in vascular endothelial cells (4,5,25,27,33).…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of nitric oxide and prostaglandins on renal escape from vasopressin-induced antidiuresis

Murase¹,

Tian²,

Fang

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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Recent results from our laboratories indicate that renal escape from AVP-induced antidiuresis is accompanied by marked downregulation of kidney aquaporin-2 (AQP2) and AVP V2 receptors. The present studies evaluated the effect of nitric oxide (NO) and PG synthesis blockade on escape from antidiuresis. dDAVP-infused rats were water loaded (WL) for 5 days. l-NAME, an NO synthesis inhibitor, or diclofenac, a cyclooxygenase inhibitor, was infused subcutaneously beginning 1 day before WL. As early as 2 days after WL, urine volume increased and urine osmolality decreased, indicating the onset of escape. Endogenous NO synthesis, measured as urinary NO2 + NO3 excretion, was significantly increased in the WL group compared with the non-WL controls during all 5 days of WL. l-NAME (20 mg. kg(-1). day(-1)) markedly decreased urine volume on days 4 and 5 of WL, indicating inhibition of the escape phenomenon. Kidney AQP2 protein was significantly increased by this dose of l-NAME as well. A lower dose of l-NAME (10 mg. kg(-1). day(-1)) or diclofenac (2.5 mg. kg(-1). day(-1)) did not significantly affect the escape phenomenon by itself, but the combination of l-NAME and diclofenac showed a marked inhibitory effect on the escape phenomenon, which was also accompanied by a significant increase in kidney AQP2 expression. These results therefore suggest that renal NO and PG both play important roles in escape from AVP-induced antidiuresis by acting synergistically to downregulate kidney AQP2 expression.

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“…In the best-characterized animal model of chronic renal failure, the subtotally nephrectomized rat, increased glomerular capillary pressure (as little as 20%) triggers MC responses that ultimately result in glomerulosclerosis (10,11,31). In vitro studies of the application of cyclic mechanical strain to MC have demonstrated that this stimulus results in MC proliferation (2,32,33) and production of collagenous protein (2) and fibronectin (12).…”

Section: Discussionmentioning

confidence: 99%

“…Initial experiments using this methodology showed induction of mRNA for the proto-oncogene and AP-1 transcription factor component c-fos at 30 min (1). Subsequently, increases in both MC proliferation (2) and collagenous and non-collagenous extracellular matrix protein synthesis were observed by 48 h, the sine qua non of sclerotic injury (10,11).…”

Section: Glomerular Mesangial Cells (Mc)mentioning

confidence: 99%

NO Inhibits Stretch-induced MAPK Activity by Cytoskeletal Disruption

Ingram¹,

James²,

Cai³

et al. 2000

Journal of Biological Chemistry

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Mesangial cells (MC) grown on extracellular matrix protein-coated plates and exposed to cyclic strain/relaxation proliferate and produce extracellular matrix protein, providing an in vitro model of signaling in stretched MC. Intracellular transduction of mechanical strain involves mitogen-activated protein kinases, and we have shown that p42/44 mitogen-activated protein kinase (extracellular signal-regulated kinase (ERK)) is activated by cyclic strain in MC. In vivo studies show that increased production of nitric oxide (NO) in the remnant kidney limits glomerular injury without reducing glomerular capillary pressure, and we have observed that NO attenuates stretch-induced ERK activity in MC via generation of cyclic guanosine monophosphate (cGMP). Accordingly, we sought to determine whether NO affects strain-induced ERK activity after strain and how this is mediated. Strain-induced ERK activity was dependent on time and magnitude of stretch and was maximal after 10 min at ؊27 kilopascals. Actin cytoskeleton disruption with cytochalasin D abrogated this. The non-metabolizable cGMP analogue 8-bromo cyclic GMP (8-Br-cGMP) dose-dependently attenuated strain-induced ERK activity. Cytoskeletal stabilization with jasplakinolide prevented this inhibitory effect of 8-Br-cGMP. Cyclic strain increased nuclear translocation of phospho-ERK by immunofluorescent microscopy, again attenuated by 8-Br-cGMP. Jasplakinolide prevented the inhibitory effect of 8-Br-cGMP on activated ERK nuclear translocation after strain. Strain increased ERK-dependent AP-1 nuclear protein binding, which was attenuated by cytochalasin D and 8-Br-cGMP. These data indicate that cGMP can inhibit cyclic strain-induced ERK activity, nuclear translocation, and AP-1 nuclear protein binding. Cytoskeletal disruption leads to the same effect, whereas cytoskeleton stabilization reverses the effect of 8-Br-cGMP. Thus, NO inhibits straininduced ERK activity by cytoskeletal destabilization.Glomerular mesangial cells (MC) 1 are positioned as architectural supports for capillary loops and are therefore exposed to pulsatile stretch/relaxation (1). Whereas little resident glomerular cell proliferation or sclerosis is demonstrable in normal animals (2), MC proliferation and matrix production, eventually resulting in sclerosis, can be induced by maneuvers that increase intraglomerular pressure by 10 mmHg (3-5). Moreover, in these models, preventing the intraglomerular pressure rise attenuates sclerosis (5-7). We and others have shown reduction of sclerosis and MC proliferation in remnant glomeruli by oral L-arginine supplementation to increase NO production (8, 9). L-Arginine increases nitric oxide production by the remnant kidney and reduces glomerular endothelin-1 expression but does not lower glomerular capillary pressure (8).The effects of mechanical forces on MC in vitro can be modelled by culturing cells in wells with deformable bottoms and then applying a vacuum to the wells to generate alternating cycles of strain and relaxation. Initial experiments using this m...

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Alteration of Cellular Function in Rat Mesangial Cells in Response to Mechanical Stretch Relaxation

Cited by 11 publications

References 0 publications

17β-Estradiol Modulates Mechanical Strain-induced MAPK Activation in Mesangial Cells

17β-Estradiol Modulates Mechanical Strain-induced MAPK Activation in Mesangial Cells

Synergistic effects of nitric oxide and prostaglandins on renal escape from vasopressin-induced antidiuresis

NO Inhibits Stretch-induced MAPK Activity by Cytoskeletal Disruption

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