Growth arrest-specific protein 1 is a novel endogenous inhibitor of glomerular cell activation and proliferation

Claudia R.C. Van Roeyen, Stephanie Zok, Jessica Pruessmeyer, Peter Boor, Yoshikuni Nagayama, Stefan Fleckenstein, Clemens D. Cohen, Frank Eitner, Hermann Josef Gröne, Tammo Ostendorf, Andreas Ludwig, Jürgen Floege

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Growth arrest-specific protein-1 (GAS1) is a GPI-anchored protein which is highly expressed in embryonic mouse fibroblasts and inhibits their proliferation. Glomerular mesangial cells release soluble GAS1 protein into the supernatant in vitro. Growth arrest led to GAS1 overexpression and increased release. Secretion involved disintegrin and metalloproteinase 10 and 17 as signified by inhibition experiments. Recombinant soluble GAS1 protein inhibited the proliferation of mesangial cells. Conversely, the induction of mesangial cell proliferation by PDGF-BB or-DD led to downregulation of GAS1 mRNA. Specific ligands of the PDGF α-receptor, PDGF-AA and-CC, had no effect. The GAS1 protein was localized in podocytes in kidneys from healthy rats. During the time course of mesangioproliferative glomerulonephritis in anti-Thy1.1-treated rats, glomerular GAS1 expression decreased prior to the onset of mesangial cell proliferation and increased at later stages during glomerular recovery. Finally, a plasmid expressing soluble GAS1 fused to an Fc fragment was systemically overexpressed in rats with mesangioproliferative glomerulonephritis. This ameliorated renal damage was indicated by decreased albuminuria and serum creatinine. Gas1/Fc-transfected rats also exhibited a reduction of the glomerular mesangial cell activation and proliferation. Thus, GAS1 is a novel endogenous inhibitor of glomerular mesangial cell proliferation and may be a novel therapeutic target in mesangioproliferative glomerular diseases.

Original languageEnglish (US)
Pages (from-to)251-263
Number of pages13
JournalKidney International
Volume83
Issue number2
DOIs
StatePublished - Feb 2013

Fingerprint

Cell Proliferation
Mesangial Cells
Growth
Proteins
Glomerulonephritis
Immunoglobulin Fc Fragments
Disintegrins
Kidney
Platelet-Derived Growth Factor Receptors
Podocytes
Albuminuria
Metalloproteases
Creatinine
Plasmids
Down-Regulation
Fibroblasts
Ligands
Messenger RNA
Serum

Keywords

  • mesangial cell
  • mesangioproliferative glomerulonephritis
  • proliferation
  • shedding

ASJC Scopus subject areas

  • Nephrology

Cite this

Van Roeyen, C. R. C., Zok, S., Pruessmeyer, J., Boor, P., Nagayama, Y., Fleckenstein, S., ... Floege, J. (2013). Growth arrest-specific protein 1 is a novel endogenous inhibitor of glomerular cell activation and proliferation. Kidney International, 83(2), 251-263. https://doi.org/10.1038/ki.2012.400

Growth arrest-specific protein 1 is a novel endogenous inhibitor of glomerular cell activation and proliferation. / Van Roeyen, Claudia R.C.; Zok, Stephanie; Pruessmeyer, Jessica; Boor, Peter; Nagayama, Yoshikuni; Fleckenstein, Stefan; Cohen, Clemens D.; Eitner, Frank; Gröne, Hermann Josef; Ostendorf, Tammo; Ludwig, Andreas; Floege, Jürgen.

In: Kidney International, Vol. 83, No. 2, 02.2013, p. 251-263.

Research output: Contribution to journalArticle

Van Roeyen, CRC, Zok, S, Pruessmeyer, J, Boor, P, Nagayama, Y, Fleckenstein, S, Cohen, CD, Eitner, F, Gröne, HJ, Ostendorf, T, Ludwig, A & Floege, J 2013, 'Growth arrest-specific protein 1 is a novel endogenous inhibitor of glomerular cell activation and proliferation', Kidney International, vol. 83, no. 2, pp. 251-263. https://doi.org/10.1038/ki.2012.400
Van Roeyen, Claudia R.C. ; Zok, Stephanie ; Pruessmeyer, Jessica ; Boor, Peter ; Nagayama, Yoshikuni ; Fleckenstein, Stefan ; Cohen, Clemens D. ; Eitner, Frank ; Gröne, Hermann Josef ; Ostendorf, Tammo ; Ludwig, Andreas ; Floege, Jürgen. / Growth arrest-specific protein 1 is a novel endogenous inhibitor of glomerular cell activation and proliferation. In: Kidney International. 2013 ; Vol. 83, No. 2. pp. 251-263.
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