title: 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.affiliation: Department of Nephrology, Hypertension, Diabetes and Endocrinology and.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, Hypertension, Diabetes and Endocrinology and.
authors.forename: Eva
authors.initials: E
authors.lastname: Sauter
authors.affiliation: Department of Nephrology, Hypertension, Diabetes and Endocrinology and.
authors.forename: Anja
authors.initials: A
authors.lastname: Schreiter
authors.affiliation: Department of Nephrology and Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany; and.
authors.forename: Claudia R C
authors.initials: CR
authors.lastname: van Roeyen
authors.affiliation: Department of Nephrology and Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany; and.
authors.forename: Tammo
authors.initials: T
authors.lastname: Ostendorf
authors.affiliation: Department of Nephrology and Immunology, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany; and.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, Dresden University of Technology, Dresden, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Gembardt
authors.affiliation: Division of Nephrology, Department of Internal Medicine III, Dresden University of Technology, Dresden, Germany.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hugo
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, Medical Faculty, Otto von Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Berend
authors.initials: B
authors.lastname: Isermann
authors.affiliation: Department of Nephrology, Hypertension, Diabetes and Endocrinology and.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Lindquist
authors.affiliation: Department of Nephrology, Hypertension, Diabetes and Endocrinology and peter.mertens@med.ovgu.de.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Mertens
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D057773:Cold Shock Proteins and Peptides / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D005920:Glomerular Mesangium / Q000473:pathology* / Q000502:physiology*; D005921:Glomerulonephritis / Q000209:etiology*; D006801:Humans; D008181:Lupus Nephritis / Q000209:etiology; D050527:Mesangial Cells / Q000473:pathology*; D051381:Rats
chemical_list: D057773:Cold Shock Proteins and Peptides; D004268:DNA-Binding Proteins
keywords: Proliferation; cell activation; cold shock proteins; mesangial cells; mesangioproliferative glomerulonephritis; platelet derived growth factor-B