Neuropilin-1 and neuropilin-2 are differentially expressed in human proteinuric nephropathies and cytokine-stimulated proximal tubular cells
- PMID: 19736548
- DOI: 10.1038/labinvest.2009.96
Neuropilin-1 and neuropilin-2 are differentially expressed in human proteinuric nephropathies and cytokine-stimulated proximal tubular cells
Abstract
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.
Similar articles
-
Neuropilin 1 and neuropilin 2 co-expression is significantly correlated with increased vascularity and poor prognosis in nonsmall cell lung carcinoma.Cancer. 2002 Nov 15;95(10):2196-201. doi: 10.1002/cncr.10936. Cancer. 2002. PMID: 12412174
-
Neuropilin-1 and neuropilin-2 act as coreceptors, potentiating proangiogenic activity.Blood. 2008 Feb 15;111(4):2036-45. doi: 10.1182/blood-2007-04-084269. Epub 2007 Dec 7. Blood. 2008. PMID: 18065694
-
Neuropilin-1 and neuropilin-2 expression in the adenoma-carcinoma sequence of colorectal cancer.Histopathology. 2013 May;62(6):908-15. doi: 10.1111/his.12098. Epub 2013 Mar 28. Histopathology. 2013. PMID: 23551578
-
The interaction of Neuropilin-1 and Neuropilin-2 with tyrosine-kinase receptors for VEGF.Adv Exp Med Biol. 2002;515:81-90. doi: 10.1007/978-1-4615-0119-0_7. Adv Exp Med Biol. 2002. PMID: 12613545 Review.
-
Neuropilins in neoplasms: expression, regulation, and function.Exp Cell Res. 2006 Mar 10;312(5):584-93. doi: 10.1016/j.yexcr.2005.11.024. Epub 2006 Jan 27. Exp Cell Res. 2006. PMID: 16445911 Review.
Cited by
-
Copy number variant scan in more than four thousand Holstein cows bred in Lombardy, Italy.PLoS One. 2024 May 21;19(5):e0303044. doi: 10.1371/journal.pone.0303044. eCollection 2024. PLoS One. 2024. PMID: 38771855 Free PMC article.
-
Deconvolution of Focal Segmental Glomerulosclerosis Pathophysiology Using Transcriptomics Techniques.Glomerular Dis. 2021 Jul 14;1(4):265-276. doi: 10.1159/000518404. eCollection 2021 Oct. Glomerular Dis. 2021. PMID: 36751384 Free PMC article. Review.
-
Neuropilin (NRPs) Related Pathological Conditions and Their Modulators.Int J Mol Sci. 2022 Jul 29;23(15):8402. doi: 10.3390/ijms23158402. Int J Mol Sci. 2022. PMID: 35955539 Free PMC article. Review.
-
Emerging Role of Neuropilin-1 and Angiotensin-Converting Enzyme-2 in Renal Carcinoma-Associated COVID-19 Pathogenesis.Infect Dis Rep. 2021 Oct 16;13(4):902-909. doi: 10.3390/idr13040081. Infect Dis Rep. 2021. PMID: 34698182 Free PMC article.
-
Single-Nucleus Transcriptomic Analysis Reveals Important Cell Cross-Talk in Diabetic Kidney Disease.Front Med (Lausanne). 2021 Apr 21;8:657956. doi: 10.3389/fmed.2021.657956. eCollection 2021. Front Med (Lausanne). 2021. PMID: 33968963 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous