Divergent effects of arginine vasopressin and angiotensin II on proliferation and expression of the immediate early genes c-fos, c-jun and Egr-1 in cultured rat glomerular mesangial cells

Schulze-Lohoff, Eckhard; Köhler, Martin; Fees, Hans; Reindl, N. J.; Rb, Sterzel

doi:10.1097/00004872-199302000-00003

Cited by 22 publications

(12 citation statements)

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“…Although AngII in many cell types exerts a predominant mitogenic activity, in some cell types, including vascular smooth muscle cells and MC, AngII inhibits cell proliferation but acts to trigger a hypertrophic response, mainly through activation of the AT 2 receptor (6,29,53,55). Accordingly, we found that AngII had no positive influence on mesangial cell proliferation but exerted a strong migratory influence on HMC, which was markedly impaired by depletion of either HuR or PKC␦ (Fig.…”

Section: Discussionmentioning

confidence: 68%

Tandem Phosphorylation of Serines 221 and 318 by Protein Kinase Cδ Coordinates mRNA Binding and Nucleocytoplasmic Shuttling of HuR

Doller

Schlepckow

Schwalbe

et al. 2010

Molecular and Cellular Biology

121

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Stabilization of mRNA by the ubiquitous RNA binding protein human antigen R (HuR), a member of the embryonic lethal abnormal vision (ELAV) protein family, requires canonical binding to AU-rich element (ARE)-bearing target mRNA and export of nuclear HuR-mRNA complexes to the cytoplasm. In human mesangial cells (HMC) both processes are induced by angiotensin II (AngII) via protein kinase Cδ (PKCδ)-triggered serine phosphorylation of HuR. By testing different point-mutated Flag-tagged HuR proteins, we found that Ser 318 within RNA recognition motif 3 (RRM3) is essential for AngII-induced binding to ARE-bearing mRNA but irrelevant for nucleocytoplasmic HuR shuttling. Conversely, mutation at Ser 221 within the HuR hinge region prevents AngII-triggered HuR export without affecting mRNA binding of HuR. Using phosphorylation state-specific antibodies, we found a transient increase in HuR phosphorylation at both serines by AngII. Functionally, PKCδ mediates the AngII-induced stabilization of prominent HuR target mRNAs, including those of cyclin A, cyclin D1, and cyclooxygenase-2 (COX-2), and is indispensable for AngII-triggered migration and wound healing of HMC. Our data suggest a regulatory paradigm wherein a simultaneous phosphorylation at different domains by PKCδ coordinates mRNA binding and nucleocytoplasmic shuttling of HuR, both of which events are essentially involved in the stabilization of HuR target mRNAs and relevant cell functions.

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Section: Discussionmentioning

confidence: 68%

Tandem Phosphorylation of Serines 221 and 318 by Protein Kinase Cδ Coordinates mRNA Binding and Nucleocytoplasmic Shuttling of HuR

Doller

Schlepckow

Schwalbe

et al. 2010

Molecular and Cellular Biology

121

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“…In the kidney, Ang II induces vasoconstric tion of the efferent arterioles to a greater degree than that of the afferent arterioles [6], resulting in glomerular hypertension and hyperfiltration and suggesting that these glomerular abnormal ities cause proliferation or sclerosis in the glo merulus [7,8], Furthermore, the glomerular mesangial cell surface has ATI receptors that are stimulated by Ang II, leading to the con striction of mesangial cells [9]. Although Ang II is thought to be involved in cell hypertrophy or proliferation in vitro, whether Ang II has a potent mitogenic activity remains controversial [10][11][12][13][14], Also, the mechanism by which the tis sue renin-angiotensin system (RAS) regulates systemic blood pressure or cell proliferation is unclear. We reported previously [15] that exog enous Ang II administration caused in vivo ex pression o f e-Jos.…”

Section: Introductionmentioning

confidence: 99%

The Angiotensin l-Converting Enzyme Inhibitor, Cilazapril Inhibits the Platelet-Derived Growth Factor B Chain Expression in Glomeruli of Spontaneously Hypertensive Rats

Yamauchi¹,

Ogura²,

Oishi³

et al. 1995

Kidney Blood Press Res

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To clarify whether in vivo expression of growth factors in the glomerulus is induced in a hypertensive animal model, we investigated the expression of platelet-derived growth factor (PDGF) B chain, transforming growth factor beta (TGF-β), and angiotensin II (Ang II) type 1 receptors in glomeruli of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. We also investigated the effects of treatment with cilazapril, an angiotensin I-converting enzyme inhibitor, on this expression. First, the expression of PDGF B chain, TGF-β, and Ang II receptors from the glomerulus were investigated using the reverse-transcriptase polymerase chain reaction in SHR and WKY rats. Although there was no significant difference in PDGF B chain, TGF-β, and Ang II receptors from the glomerulus were investigated using the reverse-transcriptase polymerase chain reaction in SHR and WKY rats. Although there was no significant difference in PDGF B chain, TGF-β or Ang 11 receptor expression between SHR and WKY rats at the age of 7 weeks, the PDGF B chain expression of 16-week-oId SHR was significantly higher (4.4-fold) than that of age-matched WKY rats. Next, we administered oral cilazapril at a dose of 10 mg/kg to 13-week-old SHR daily for 3 weeks. The systolic blood pressure in SHR treated with cilazapril was significantly lower than that in control SHR. After administration of cilazapril for 3 weeks, we examined the in vivo expression of growth factors and Ang II receptors in the glomerulus. The PDGF B chain expression was suppressed by treatment with cilazapril (2.5-fold) as compared with non-treated SHR. No alteration in TGF-β or Ang II receptor expression was detected. We did not find any histological changes in the kidneys of SHR, WKY rats or cilazapril-treated SHR, and cilazapril treatment did not suppress the glomerular size. These findings indicate that the expression of PDGF B chain in the glomerulus preceded the appearance of histological changes in SHR and that the administration of cilazapril inhibited the expression of PDGF B chain without affecting the glomerular size. This suggests that angiotensin I-converting enzyme inhibitors directly suppress the Ang II-induced PDGF B chain promotion in the glomerulus of SHR at the established hypertensive stage.

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“…Circulating vasoactive hormones, such as angiotensin II, ET‐1 and AVP, easily penetrate the highly permeable mesangial area and modulate glomerular function 23,24 . Vasopressin has been shown to cause contraction of mesangial cells 25 and it has been demonstrated that AVP also potently induces hyperplasia and stimulates the expression of early growth‐response genes in these cells 10,11 . However, there is much that remains obscure about the regulation of ECM production in mesangial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, AVP has been identified as a powerful mitogen of several cell types, including glomerular mesangial cells 8,9 . Vasopressin induces hyperplasia and hypertrophy and stimulates the expression of early growth‐response genes in mesangial cells through V 1A receptors 10,11 . This receptor is coupled, through a pertussis toxin‐insensitive G‐protein, to phosphatidylinositol‐specific phospholipase C (PLC).…”

Section: Introductionmentioning

confidence: 99%

Vasopressin Stimulates the Production of Extracellular Matrix by Cultured Rat Mesangial Cells

Tahara

Tsukada

Tomura

et al. 2007

Clin Exp Pharma Physio

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1. Mesangial expansion, an indicator of chronic glomerular diseases, occurs as a result of the excessive accumulation of extracellular matrix (ECM) proteins, such as type IV collagen. In order to investigate the ability of vasopressin (AVP), which causes mesangial cell proliferation and hypertrophy, to induce ECM production, an enzyme-linked immunosorbent assay was used to measure type I and IV collagen and fibronectin produced from cultured rat mesangial cells. 2. Addition of AVP (0.01-1000 nmol/L) caused a significant and concentration-dependent production of secreted and cell-associated ECM, type I collagen, type IV collagen and fibronectin by cultured rat mesangial cells. The AVP V(1A) receptor-selective antagonist YM218 (0.01-1000 nmol/L) potently and concentration-dependently inhibited the induced increase in ECM production caused by AVP, but the V(2) receptor-selective antagonist SR 121463A (0.1-1000 nmol/L) did not potently inhibit. 3. Vasopressin inhibited the synthesis of matrix metalloproteinase (MMP)-2, which degrades matrix proteins, including type IV collagen, and stimulated endothelin (ET)-1 secretion from mesangial cells. These effects were potently inhibited by YM218, but not by SR 121463A. 4. In addition, 10 nmol/L ET-1 inhibited the synthesis of MMP-2 and stimulated ECM production in mesangial cells. These effects were completely abolished by the ET(A) receptor-selective antagonist YM598 (1 micromol/L); however, the ET(B) receptor-selective antagonist BQ-788 (1 micromol/L) and the AVP receptor antagonists YM218 and SR 121463A did not inhibit ET-1-induced inhibition of MMP-2 synthesis and ECM production. In addition, AVP-induced inhibition of MMP-2 synthesis and ECM production were partly inhibited by YM598. 5. These findings indicate that AVP may modulate ECM production not only via a direct action on V(1A) receptors, but also through stimulation of ET-1 secretion. Vasopressin may contribute to the glomerular remodelling and ECM accumulation observed in glomerular diseases.

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Divergent effects of arginine vasopressin and angiotensin II on proliferation and expression of the immediate early genes c-fos, c-jun and Egr-1 in cultured rat glomerular mesangial cells

Cited by 22 publications

References 0 publications

Tandem Phosphorylation of Serines 221 and 318 by Protein Kinase Cδ Coordinates mRNA Binding and Nucleocytoplasmic Shuttling of HuR

Tandem Phosphorylation of Serines 221 and 318 by Protein Kinase Cδ Coordinates mRNA Binding and Nucleocytoplasmic Shuttling of HuR

The Angiotensin l-Converting Enzyme Inhibitor, Cilazapril Inhibits the Platelet-Derived Growth Factor B Chain Expression in Glomeruli of Spontaneously Hypertensive Rats

Vasopressin Stimulates the Production of Extracellular Matrix by Cultured Rat Mesangial Cells

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