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Biochem J. Mar 15, 2002; 362(Pt 3): 693–700.
PMCID: PMC1222434

Mesangial cell gelatinase A synthesis is attenuated by oscillating hyperbaric pressure.

Abstract

Glomerular hypertension has been established as a major factor contributing to glomerular scarring. Underlying cellular mechanisms leading to matrix accumulation are largely unknown. The isolated effect of oscillating hyperbaric pressure [OP; P(max) 50 mmHg (1 mmHg=0.133 kPa), P(mean) 24 mmHg, with a fixed oscillation of 60/min] on matrix-degrading protease secretion by rat mesangial cells (MCs) was analysed using a pressure chamber model described previously [Mertens, Espenkott, Venjakob, Heintz, Handt and Sieberth (1998) Hypertension 32, 945-952]. MCs were grown under atmospheric pressure (AP) or a controlled OP, and protease synthesis and gene transcription were analysed. A distinct biphasic cellular response to OP with stimulated gelatinase A protein expression and enzyme activity during the initial 24 h, and subsequent inhibition, was apparent, as shown by gelatin zymography. Gelatinase B activity remained unchanged. The abundance of gelatinase A transcripts, determined by reverse transcriptase-PCR, indicated a concordant regulation of gene transcription. To elucidate underlying regulatory events, reporter constructs were transfected. In these experiments, a recently identified response element, RE-1, conferred a significant stimulatory effect within the initial 4 h of OP. Nuclear protein/RE-1 binding studies revealed additional complexes from 5 min up to 3 h after OP exposure, with intensities dependent on P(max). STAT3 was identified as a component of these novel complexes. Down-regulation of cis-activity after 48 h of OP exposure was not transferred via the proximal 1686 bp of the gelatinase A regulatory sequence. In conclusion, hyperbaric OP elicits time-dependent changes in rat MC gelatinase A gene transcription.

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Selected References

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  • Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med. 1982 Sep 9;307(11):652–659. [PubMed]
  • Hostetter TH, Rennke HG, Brenner BM. Compensatory renal hemodynamic injury: a final common pathway of residual nephron destruction. Am J Kidney Dis. 1982 Mar;1(5):310–314. [PubMed]
  • Klahr S, Schreiner G, Ichikawa I. The progression of renal disease. N Engl J Med. 1988 Jun 23;318(25):1657–1666. [PubMed]
  • Riser BL, Cortes P, Zhao X, Bernstein J, Dumler F, Narins RG. Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat. J Clin Invest. 1992 Nov;90(5):1932–1943. [PMC free article] [PubMed]
  • Pelayo JC, Westcott JY. Impaired autoregulation of glomerular capillary hydrostatic pressure in the rat remnant nephron. J Clin Invest. 1991 Jul;88(1):101–105. [PMC free article] [PubMed]
  • Lovett DH, Johnson RJ, Marti HP, Martin J, Davies M, Couser WG. Structural characterization of the mesangial cell type IV collagenase and enhanced expression in a model of immune complex-mediated glomerulonephritis. Am J Pathol. 1992 Jul;141(1):85–98. [PMC free article] [PubMed]
  • Harendza S, Behrens U, Zahner G, Schneider A, Stahl RA. In vitro characterization of the mesangial phenotype in a proliferative glomerulonephritis of the rat. Nephrol Dial Transplant. 1997 Dec;12(12):2537–2541. [PubMed]
  • Steinmann-Niggli K, Ziswiler R, Küng M, Marti HP. Inhibition of matrix metalloproteinases attenuates anti-Thy1.1 nephritis. J Am Soc Nephrol. 1998 Mar;9(3):397–407. [PubMed]
  • Turck J, Pollock AS, Lee LK, Marti HP, Lovett DH. Matrix metalloproteinase 2 (gelatinase A) regulates glomerular mesangial cell proliferation and differentiation. J Biol Chem. 1996 Jun 21;271(25):15074–15083. [PubMed]
  • Border WA, Okuda S, Nakamura T. Extracellular matrix and glomerular disease. Semin Nephrol. 1989 Dec;9(4):307–317. [PubMed]
  • Floege J, Burns MW, Alpers CE, Yoshimura A, Pritzl P, Gordon K, Seifert RA, Bowen-Pope DF, Couser WG, Johnson RJ. Glomerular cell proliferation and PDGF expression precede glomerulosclerosis in the remnant kidney model. Kidney Int. 1992 Feb;41(2):297–309. [PubMed]
  • Floege J, Eng E, Lindner V, Alpers CE, Young BA, Reidy MA, Johnson RJ. Rat glomerular mesangial cells synthesize basic fibroblast growth factor. Release, upregulated synthesis, and mitogenicity in mesangial proliferative glomerulonephritis. J Clin Invest. 1992 Dec;90(6):2362–2369. [PMC free article] [PubMed]
  • Riser BL, Cortes P, Yee J, Sharba AK, Asano K, Rodriguez-Barbero A, Narins RG. Mechanical strain- and high glucose-induced alterations in mesangial cell collagen metabolism: role of TGF-beta. J Am Soc Nephrol. 1998 May;9(5):827–836. [PubMed]
  • Cortes P, Riser BL, Yee J, Narins RG. Mechanical strain of glomerular mesangial cells in the pathogenesis of glomerulosclerosis: clinical implications. Nephrol Dial Transplant. 1999 Jun;14(6):1351–1354. [PubMed]
  • Cortes P, Riser BL, Zhao X, Narins RG. Glomerular volume expansion and mesangial cell mechanical strain: mediators of glomerular pressure injury. Kidney Int Suppl. 1994 Feb;45:S11–S16. [PubMed]
  • Homma T, Akai Y, Burns KD, Harris RC. Activation of S6 kinase by repeated cycles of stretching and relaxation in rat glomerular mesangial cells. Evidence for involvement of protein kinase C. J Biol Chem. 1992 Nov 15;267(32):23129–23135. [PubMed]
  • Raghow R, Thompson JP. Molecular mechanisms of collagen gene expression. Mol Cell Biochem. 1989 Mar 16;86(1):5–18. [PubMed]
  • Riser BL, Cortes P, Heilig C, Grondin J, Ladson-Wofford S, Patterson D, Narins RG. Cyclic stretching force selectively up-regulates transforming growth factor-beta isoforms in cultured rat mesangial cells. Am J Pathol. 1996 Jun;148(6):1915–1923. [PMC free article] [PubMed]
  • Yasuda T, Kondo S, Homma T, Harris RC. Regulation of extracellular matrix by mechanical stress in rat glomerular mesangial cells. J Clin Invest. 1996 Nov 1;98(9):1991–2000. [PMC free article] [PubMed]
  • Ingram AJ, Scholey JW. Stress-responsive signal transduction mechanisms in glomerular cells. Curr Opin Nephrol Hypertens. 2000 Jan;9(1):49–55. [PubMed]
  • Riser BL, Cortes P, Yee J. Modelling the effects of vascular stress in mesangial cells. Curr Opin Nephrol Hypertens. 2000 Jan;9(1):43–47. [PubMed]
  • Kawata Y, Mizukami Y, Fujii Z, Sakumura T, Yoshida K, Matsuzaki M. Applied pressure enhances cell proliferation through mitogen-activated protein kinase activation in mesangial cells. J Biol Chem. 1998 Jul 3;273(27):16905–16912. [PubMed]
  • Mertens PR, Espenkott V, Venjakob B, Heintz B, Handt S, Sieberth HG. Pressure oscillation regulates human mesangial cell growth and collagen synthesis. Hypertension. 1998 Nov;32(5):945–952. [PubMed]
  • Singal DP, Qiu X. Polymorphism in both X and Y box motifs controls level of expression of HLA-DRB1 genes. Immunogenetics. 1996;43(1-2):50–56. [PubMed]
  • Singhal PC, Gibbons N, Franki N, Reddy K, Sharma P, Mattana J, Wagner JD, Bansal V. Simulated glomerular hypertension promotes mesangial cell apoptosis and expression of cathepsin-B and SGP-2. J Investig Med. 1998 Feb;46(2):42–50. [PubMed]
  • Ailenberg M, Silverman M. Cellular activation of mesangial gelatinase A by cytochalasin D is accompanied by enhanced mRNA expression of both gelatinase A and its membrane-associated gelatinase A activator (MT-MMP). Biochem J. 1996 Feb 1;313(Pt 3):879–884. [PMC free article] [PubMed]
  • Zhong H, Simons JW. Direct comparison of GAPDH, beta-actin, cyclophilin, and 28S rRNA as internal standards for quantifying RNA levels under hypoxia. Biochem Biophys Res Commun. 1999 Jun 16;259(3):523–526. [PubMed]
  • Mertens PR, Harendza S, Pollock AS, Lovett DH. Glomerular mesangial cell-specific transactivation of matrix metalloproteinase 2 transcription is mediated by YB-1. J Biol Chem. 1997 Sep 5;272(36):22905–22912. [PubMed]
  • Mertens PR, Alfonso-Jaume MA, Steinmann K, Lovett DH. A synergistic interaction of transcription factors AP2 and YB-1 regulates gelatinase A enhancer-dependent transcription. J Biol Chem. 1998 Dec 4;273(49):32957–32965. [PubMed]
  • Mertens PR, Alfonso-Jaume MA, Steinmann K, Lovett DH. YB-1 regulation of the human and rat gelatinase A genes via similar enhancer elements. J Am Soc Nephrol. 1999 Dec;10(12):2480–2487. [PubMed]
  • Harendza S, Pollock AS, Mertens PR, Lovett DH. Tissue-specific enhancer-promoter interactions regulate high level constitutive expression of matrix metalloproteinase 2 by glomerular mesangial cells. J Biol Chem. 1995 Aug 11;270(32):18786–18796. [PubMed]
  • Haan S, Kortylewski M, Behrmann I, Müller-Esterl W, Heinrich PC, Schaper F. Cytoplasmic STAT proteins associate prior to activation. Biochem J. 2000 Feb 1;345(Pt 3):417–421. [PMC free article] [PubMed]
  • Wegenka UM, Lütticken C, Buschmann J, Yuan J, Lottspeich F, Müller-Esterl W, Schindler C, Roeb E, Heinrich PC, Horn F. The interleukin-6-activated acute-phase response factor is antigenically and functionally related to members of the signal transducer and activator of transcription (STAT) family. Mol Cell Biol. 1994 May;14(5):3186–3196. [PMC free article] [PubMed]
  • Ehret GB, Reichenbach P, Schindler U, Horvath CM, Fritz S, Nabholz M, Bucher P. DNA binding specificity of different STAT proteins. Comparison of in vitro specificity with natural target sites. J Biol Chem. 2001 Mar 2;276(9):6675–6688. [PubMed]
  • Singhal PC, Sagar S, Garg P. Simulated glomerular pressure modulates mesangial cell 72 kDa metalloproteinase activity. Connect Tissue Res. 1996;33(4):257–263. [PubMed]
  • Bian J, Sun Y. Transcriptional activation by p53 of the human type IV collagenase (gelatinase A or matrix metalloproteinase 2) promoter. Mol Cell Biol. 1997 Nov;17(11):6330–6338. [PMC free article] [PubMed]
  • Kawata Y, Fujii Z, Sakumura T, Kitano M, Suzuki N, Matsuzaki M. High pressure conditions promote the proliferation of rat cultured mesangial cells in vitro. Biochim Biophys Acta. 1998 Feb 4;1401(2):195–202. [PubMed]
  • Gatsios P, Terstegen L, Schliess F, Häussinger D, Kerr IM, Heinrich PC, Graeve L. Activation of the Janus kinase/signal transducer and activator of transcription pathway by osmotic shock. J Biol Chem. 1998 Sep 4;273(36):22962–22968. [PubMed]
  • Bode JG, Gatsios P, Ludwig S, Rapp UR, Häussinger D, Heinrich PC, Graeve L. The mitogen-activated protein (MAP) kinase p38 and its upstream activator MAP kinase kinase 6 are involved in the activation of signal transducer and activator of transcription by hyperosmolarity. J Biol Chem. 1999 Oct 15;274(42):30222–30227. [PubMed]
  • Shinoki N, Kawasaki T, Minamino N, Okahara K, Ogawa A, Ariyoshi H, Sakon M, Kambayashi J, Kangawa K, Monden M. Shear stress down-regulates gene transcription and production of adrenomedullin in human aortic endothelial cells. J Cell Biochem. 1998 Oct 1;71(1):109–115. [PubMed]
  • Resnick N, Collins T, Atkinson W, Bonthron DT, Dewey CF, Jr, Gimbrone MA., Jr Platelet-derived growth factor B chain promoter contains a cis-acting fluid shear-stress-responsive element. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4591–4595. [PMC free article] [PubMed]
  • Saarialho-Kere UK, Welgus HG, Parks WC. Distinct mechanisms regulate interstitial collagenase and 92-kDa gelatinase expression in human monocytic-like cells exposed to bacterial endotoxin. J Biol Chem. 1993 Aug 15;268(23):17354–17361. [PubMed]
  • Sadoshima J, Izumo S. The cellular and molecular response of cardiac myocytes to mechanical stress. Annu Rev Physiol. 1997;59:551–571. [PubMed]
  • Ingram AJ, Ly H, Thai K, Kang M, Scholey JW. Activation of mesangial cell signaling cascades in response to mechanical strain. Kidney Int. 1999 Feb;55(2):476–485. [PubMed]
  • Khachigian LM, Resnick N, Gimbrone MA, Jr, Collins T. Nuclear factor-kappa B interacts functionally with the platelet-derived growth factor B-chain shear-stress response element in vascular endothelial cells exposed to fluid shear stress. J Clin Invest. 1995 Aug;96(2):1169–1175. [PMC free article] [PubMed]
  • Komuro I, Kaida T, Shibazaki Y, Kurabayashi M, Katoh Y, Hoh E, Takaku F, Yazaki Y. Stretching cardiac myocytes stimulates protooncogene expression. J Biol Chem. 1990 Mar 5;265(7):3595–3598. [PubMed]
  • Sadoshima J, Jahn L, Takahashi T, Kulik TJ, Izumo S. Molecular characterization of the stretch-induced adaptation of cultured cardiac cells. An in vitro model of load-induced cardiac hypertrophy. J Biol Chem. 1992 May 25;267(15):10551–10560. [PubMed]
  • Harendza S, Lovett DH, Stahl RA. The hematopoietic transcription factor PU.1 represses gelatinase A transcription in glomerular mesangial cells. J Biol Chem. 2000 Jun 30;275(26):19552–19559. [PubMed]

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