Cold Shock Proteins Mediate GN with Mesangioproliferation.

Abstract

DNA binding protein A (DbpA) is a member of the human cold shock domain-containing protein superfamily, with known functions in cell proliferation, differentiation, and stress responses. DbpA mediates tight junction-associated activities in tubular epithelial cells, but the function of DbpA in mesangial cells is unknown. Here, we found DbpA protein expression restricted to vascular smooth muscle cells in healthy human kidney tissue but profound induction of DbpA protein expression within the glomerular mesangial compartment in mesangioproliferative nephritis. In vitro, depletion or overexpression of DbpA using lentiviral constructs led to inhibition or promotion, respectively, of mesangial cell proliferation. Because platelet-derived growth factor B (PDGF-B) signaling has a pivotal role in mesangial cell proliferation, we examined the regulatory effect of PDGF-B on DbpA. In vitro studies of human and rat mesangial cells confirmed a stimulatory effect of PDGF-B on DbpA transcript numbers and protein levels. Additional in vivo investigations showed DbpA upregulation in experimental rat anti-Thy1.1 nephritis and murine mesangioproliferative nephritis models. To interfere with PDGF-B signaling, we injected nephritic rats with PDGF-B neutralizing aptamers or the MEK/ERK inhibitor U0126. Both interventions markedly decreased DbpA protein expression. Conversely, continuous PDGF-B infusion in healthy rats induced DbpA expression predominantly within the mesangial compartment. Taken together, these results indicate that DbpA is a novel target of PDGF-B signaling and a key mediator of mesangial cell proliferation.

• Authors: Cheng Zhu, Eva Sauter, Anja Schreiter, Claudia R C van Roeyen, Tammo Ostendorf, Jürgen Floege, Florian Gembardt, Christian P Hugo, Berend Isermann, Jonathan A Lindquist, Peter R Mertens
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 27 Issue 12 Pg. 3678-3689 (Dec 2016) ISSN: 1533-3450 [Electronic] United States
• PMID: 27151923 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 by the American Society of Nephrology.

Chemical References

• Cold Shock Proteins and Peptides
• DNA-Binding Proteins

Topics

• Animals
• Cell Proliferation
• Cells, Cultured
• Cold Shock Proteins and Peptides (physiology)
• DNA-Binding Proteins (physiology)
• Glomerular Mesangium (pathology, physiology)
• Glomerulonephritis (etiology)
• Humans
• Lupus Nephritis (etiology)
• Mesangial Cells (pathology)
• Rats