Hyperosmotic Stress Stimulates Promoter Activity and Regulates Cellular Utilization of the Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by a p38 MAPK-dependent Pathway

Bell, L. M.; Leong, Meredith L.; Kim, Brian; Edward, Wang; Park, Jongsun; Hemmings, Brian A.; Firestone, Gary L.

doi:10.1074/jbc.m002076200

Cited by 143 publications

(157 citation statements)

References 80 publications

(79 reference statements)

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“…In this fish, OSTF1 mRNA and protein levels rapidly increased in response to hyperosmotic stress. This finding is reminiscent of SGK1, which is also regulated by both aldosterone and osmotic stress in kidney collecting duct cells (38) and other cell types as well (39,40). The rapid activation kinetics is again characteristic of immediate early genes like SGK1.…”

Section: Discussionmentioning

confidence: 71%

Differential Activities of Glucocorticoid-induced Leucine Zipper Protein Isoforms

Soundararajan

Wang

Melters

et al. 2007

Journal of Biological Chemistry

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Glucocorticoid-induced leucine zipper protein (GILZ) is expressed in both epithelial and immune tissues and modulates a variety of cellular functions, including proliferation and epithelial sodium channel (ENaC) activity. A number of reports have described various GILZ activities, focusing on a single isoform with molecular mass of ϳ17 kDa, now termed GILZ1. In GILZ immunoblots using a newly developed antiserum, we detected multiple species in extracts from cultured kidney cells. Mass spectrometric analysis revealed that one of these represented a previously uncharacterized distinct isoform of GILZ, GILZ2. Rapid amplification of cDNA ends was used to clone cDNAs corresponding to four isoforms, which, in addition to GILZ1 and GILZ2, included new isoforms GILZ3 and GILZ4. Heterologous expression of these four GILZ isoforms in cultured cells revealed striking functional differences. Notably, GILZ1 was the only isoform that significantly stimulated ENaCmediated Na ؉ current in a kidney collecting duct cell line, although GILZ2 and GILZ3 also stimulated ENaC surface expression in HEK 293 cells. GILZ1 and GILZ3, and to a lesser extent GILZ2, inhibited ERK phosphorylation. Interestingly, GILZ4, which had no effect on either ENaC or ERK, potently suppressed cellular proliferation, as did GILZ1, but not GILZ2 or GILZ3. Finally, rat and mouse tissues all expressed multiple GILZ species but varied in the relative abundance of each. These data suggest that multiple GILZ isoforms are expressed in most cells and tissues and that these play distinct roles in regulating key cellular functions, including proliferation and ion transport. Furthermore, GILZ inhibition of ERK appears to play an essential role in stimulation of cell surface ENaC but not in inhibition of proliferation. Glucocorticoid-induced leucine zipper (GILZ)3 is a small leucine zipper protein of ϳ17 kDa. As its name implies, GILZ was first discovered as a dexamethasone-induced transcript in murine thymocytes, which it protects from apoptosis induced by treatment with anti-CD3 antibody (1). It is a member of the TSC22D (transforming growth factor ␤1-stimulated clone 22 domain) family of proteins that are widely expressed and appear to impact multiple biological processes (2-5). TSC22D1 (or, simply, TSC22) was first isolated based on its rapid and transient transcriptional induction by transforming growth factor ␤1 (6). It is a potential tumor suppressor gene and has been shown to down-regulate cell proliferation and induce apoptosis in human salivary gland (7,8). Its expression in human fetal tissues (9) and, more recently, its detection at sites of epithelial-mesenchymal interactions during mouse embryogenesis (10) suggest an important role for this protein during vertebrate development. A similar role has been identified for the TSC22 homologue, bunched, in developing Drosophila larvae (11). TSC22D2 and TSC22D4 are expressed in renal cortex, medulla, and papilla and are involved in adaptation of these cells to hypertonicity (4). These two transcripts are signifi...

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Section: Discussionmentioning

confidence: 71%

Differential Activities of Glucocorticoid-induced Leucine Zipper Protein Isoforms

Soundararajan

Wang

Melters

et al. 2007

Journal of Biological Chemistry

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“…Proliferation can be regulated by the extracellular matrix, 23 by morphogenic factors, 24 and by acute physiological parameters. 25,26 The morphogenic influences that initiate differentiation by halting mitosis as well as the subsequent mechanisms that control functional tissue development are not known so far. 27 Functional tissue regeneration must be reevaluated-for example, why can fractured bone quickly regain its function by repair while neighboring cartilage can only produce fibrous repair tissue and remains functionally crippled?…”

Section: Why Proliferation Rates Differmentioning

confidence: 99%

Proliferating Cells versus Differentiated Cells in Tissue Engineering

et al. 2002

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The efficiency of cell or tissue cultures is usually judged by how quickly confluence is reached within a Petri dish or on a scaffold. Growth factors and fetal bovine serum are employed to drive cultured cells from one mitosis to the next as quickly as possible. The tissue specific interphase is extremely short under these conditions, so that the degree of differentiation desired in tissue engineering cannot be achieved. To reach the goal of functional differentiation in vitro mitosis and interphase must be separated experimentally and tailored to the specific requirements of the cell-type used. This could be achieved by a three step concept for tissue-engineering in vitro as we present here. The expansion phase is followed by a phase in which tissue differentiation is initiated. The final phase serves to express and maintain histotypical differentiation of the generated tissue.

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“…10 This kinase appears to be a signaling intermediate linking aldosterone and insulin to increased sodium reabsorption in the collecting duct of the kidney. Sgk1 has previously been shown to respond to osmotic stimuli in hepatic epithelial cells as well as a variety of other cell types, [11][12][13] leading us to hypothesize that this kinase might serve as an intermediary in the osmotic induction of NPR-A gene expression in IMCD cells. Our studies confirm that Sgk1 is expressed in cultured rat IMCD cells, that this expression is induced by increased extracellular osmolality, and that this, in turn, appears to be linked to the increase in NPR-A gene promoter activity, albeit through an eNOS-independent pathway.…”

mentioning

confidence: 99%

Sgk1 Mediates Osmotic Induction of NPR-A Gene in Rat Inner Medullary Collecting Duct Cells

Chen¹,

McCormick²,

Prabaker³

et al. 2004

Hypertension

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Abstract-We have shown previously that increased extracellular osmolality stimulates expression and promoter activity of the type A natriuretic peptide receptor (NPR-A) gene in rat inner medullary collecting duct (IMCD) cells through a mechanism that involves activation of p38 mitogen-activated protein kinase (MAPK). The serum and glucocorticoid inducible kinase (Sgk) is thought to participate in the regulation of sodium handling in distal tubular segments. We sought to determine whether this kinase might be involved in the osmotic stimulation of NPR-A gene promoter activity. Exposure of cultured IMCD cells to an additional 75 mmol/L NaCl in culture media (final osmolality 475 mosm/kg) resulted in an Ϸ4-fold increase in Sgk1 protein levels after 7 hours. The Sgk1 induction was almost completely inhibited by the p38 MAPK inhibitor SB203580, indicating that NaCl activates Sgk1 through the p38 MAPK pathway. Transient transfection of a mouse Sgk1 expression vector along with a Ϫ1590 NPR-A luciferase reporter resulted in an Ϸ3-fold increment in reporter activity, which was significantly reduced by cotransfection with a kinase-dead Sgk1 mutant. The NaCl-dependent induction was partially blocked (Ϸ40% inhibition) by cotransfection of the kinase-dead Sgk1 mutant. Neither Sgk1 nor the kinase-dead mutant had any effect on endothelial nitric oxide synthase (eNOS) promoter activity, and the Sgk1 mutant and 8-bromo-cyclic guanosine monophosphate were, to some degree, additive in reducing osmotically stimulated NPR-A promoter activity. Collectively, these data imply that Sgk1 operates over an eNOS-independent, p38 MAPK-dependent pathway in mediating osmotic induction of the NPR-A gene promoter. Key Words: glucocorticoids Ⅲ kinase Ⅲ receptors Ⅲ atrial natriuretic factor Ⅲ gene regulation Ⅲ signal transduction T he inner medullary collecting duct is the terminal nephron segment responsible for the final regulation of urinary sodium content. It is the target of several hormonal systems that promote either sodium retention or sodium excretion. 1 The natriuretic peptides are a family of peptide hormones that promote a natriuretic diuresis in the kidney through a combination of vasoregulatory properties and direct effects on sodium transport in the collecting duct epithelial cell. 2 There are 3 types of natriuretic peptides and 3 classes of receptors that signal their activities. Atrial natriuretic peptide and brain natriuretic peptide are produced primarily in the heart (atria and ventricles, respectively), whereas C type natriuretic peptide is produced in a variety of extracardiac tissues including the vascular endothelium. Atrial natriuretic peptide and brain natriuretic peptide interact primarily with the type A natriuretic peptide receptor (NPR-A), whereas C type natriuretic peptide binds to and activates the type B receptor (NPR-B). 2 Each of these receptors is a particulate guanylyl cyclase. Occupancy of the receptor by ligand increases cyclase activity and, thereby, increases cyclic GMP levels in the target cell. In the kid...

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Hyperosmotic Stress Stimulates Promoter Activity and Regulates Cellular Utilization of the Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by a p38 MAPK-dependent Pathway

Cited by 143 publications

References 80 publications

Differential Activities of Glucocorticoid-induced Leucine Zipper Protein Isoforms

Differential Activities of Glucocorticoid-induced Leucine Zipper Protein Isoforms

Proliferating Cells versus Differentiated Cells in Tissue Engineering

Sgk1 Mediates Osmotic Induction of NPR-A Gene in Rat Inner Medullary Collecting Duct Cells

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