Neuropilin-1 and neuropilin-2 are differentially expressed in human proteinuric nephropathies and cytokine-stimulated proximal tubular cells

Autor: Michael A. Rudnicki, Rita Sarközi, Christina Lauterberg, Rudolf Albrecht, Markus Pirklbauer, Gert Mayer, Frank Strutz, Herbert Schramek, Susie-Jane Noppert, Andreas Kronbichler, Paul Perco
Rok vydání: 2009
Předmět:
Male
medicine.medical_specialty
Neuropilins
medicine.medical_treatment
Interleukin-1beta
Gene Expression
Oncostatin M
Glomerulonephritis
Membranous
Pathology and Forensic Medicine
Kidney Tubules
Proximal
Transforming Growth Factor beta1
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
Internal medicine
Neuropilin 1
Neuropilin
medicine
Humans
RNA
Messenger
Fluorescent Antibody Technique
Indirect
Molecular Biology
Cells
Cultured
Aged
030304 developmental biology
0303 health sciences
biology
Glomerulosclerosis
Focal Segmental
Growth factor
Cell Biology
Middle Aged
Prognosis
Fibrosis
Neuropilin-1
Neuropilin-2
Up-Regulation
Vascular endothelial growth factor
Endocrinology
chemistry
030220 oncology & carcinogenesis
Cancer research
biology.protein
Female
Hepatocyte growth factor
Glomerular Filtration Rate
medicine.drug
Zdroj: Laboratory Investigation. 89:1304-1316
ISSN: 0023-6837
DOI: 10.1038/labinvest.2009.96
Popis: Neuropilin-1 (NRP1) and neuropilin-2 (NRP2) are transmembrane glycoproteins with large extracellular domains that interact with class 3 semaphorins, vascular endothelial growth factor (VEGF) family members, and ligands, such as hepatocyte growth factor, platelet-derived growth factor BB, transforming growth factor-beta1 (TGF-beta1), and fibroblast growth factor2 (FGF2). Neuropilins (NRPs) have been implicated in tumor growth and vascularization, as novel mediators of the primary immune response and in regeneration and repair; however, their role in renal pathophysiology is largely unknown. Here, we report upregulation of tubular and interstitial NRP2 protein expression in patients with focal segmental glomerulosclerosis (FSGS). In an additional cohort of patients with minimal change disease (MCD), membranous nephropathy (MN), and FSGS, elevated NRP2 mRNA expression in kidney biopsies inversely correlated with estimated glomerular filtration rate (eGFR) at the time of biopsy. Furthermore, upregulation of NRP2 mRNA correlated with post-bioptic decline of kidney function. Expression of NRP1 and NRP2 in human proximal tubular cells (PTCs) was differentially affected after stimulation with TGF-beta1, interleukin-1beta (IL-1beta), and oncostatin M (OSM). Although the pro-fibrotic mediators, TGF-beta1 and IL-1beta, induced upregulation of NRP2 expression but downregulation of NRP1 expression, OSM stimulated the expression of both NRP1 and NRP2. Basal and OSM-induced NRP1 mRNA expression, as well as TGF-beta1-induced NRP2 mRNA and protein expression were partially mediated by MEK1/2-ERK1/2 signaling. This is the first report suggesting a differential role of NRP1 and NRP2 in renal fibrogenesis, and TGF-beta1, IL-1beta, and OSM represent the first ligands known to stimulate NRP2 expression in mammalian cells.
Databáze: OpenAIRE
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