Dataset Information

Citrullination of latency-associated peptide of TGF beta1

ABSTRACT: Enzymatic citrullination of latency-associated peptide of TGF beta1 by PAD2

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Dr Jyrki Heino

PROVIDER: MSV000080224 | MassIVE | Tue Oct 04 14:26:00 BST 2016

SECONDARY ACCESSION(S): PXD003132

REPOSITORIES: MassIVE

ACCESS DATA

Publications

Extracellular citrullination inhibits the function of matrix associated TGF-β.

Sipilä Kalle H KH Ranga Vipin V Rappu Pekka P Torittu Annamari A Pirilä Laura L Käpylä Jarmo J Johnson Mark S MS Larjava Hannu H Heino Jyrki J

Matrix biology : journal of the International Society for Matrix Biology 20160303

In inflammatory arthritis peptidyl arginine deiminase (PAD) enzymes can citrullinate arginine residues in extracellular matrix (ECM) proteins, such as collagens and fibronectin. This may lead to the generation of anti-citrullinated protein antibodies, important diagnostic markers in rheumatoid arthritis. In addition, the citrullination may directly affect protein function. Based on structural analysis, we found that most ECM-associated growth factors (GFs) have arginine residues in their recepto ...[more]

PMID: 26923761

Similar Datasets

Project description:Microarray analysis reveals up-regulation of retinoic acid and hepatocyte growth factor related signaling pathways by pro-insulin C-peptide in kidney proximal tubular cells: Antagonism of the pro-fibrotic effects of TGF-b1 Novel signaling roles for C-peptide have recently been discovered with evidence that it can ameliorate complications of type 1 diabetes. Here we sought to identify new pathways regulated by C-peptide of relevance to the pathophysiology of diabetic nephropathy. Microarray analysis was performed to identify genes regulated by either C-peptide and/or transforming growth factor beta 1 (TGF-β1) in a human proximal tubular cell line, HK-2. Expression of retinoic acid receptor β (RARβ), hepatcoyte growth factor (HGF), cellular retinoic acid binding protein II (CRABPII), vimentin, E-cadherin, Snail and β-catenin was assessed by immunoblotting. The cellular localisation of vimentin and β-catenin was determined by immunocytochemistry. Changes in cell morphology were assessed by phase contrast microscopy. Gene expression profiling demonstrated differential expression of 953 and 1,458 genes after C-peptide exposure for 18h or 48h respectively. From these, members of the anti-fibrotic retinoic acid (RA) and HGF signaling pathways were selected. Immunoblotting demonstrated that C-peptide increased RARβ, CRABPII and HGF. We confirmed a role for RA in reversal of TGF-β1-induced changes associated with epithelial-mesenchymal transition (EMT), including expression changes in Snail, E-cadherin, vimetin and redistribution of β-catenin. Importantly, these TGF-β1-induced changes were inhibited by C-peptide. Further, effects of TGF-β1 on Snail and E-cadherin expression were blocked by HGF and inhibitory effects of C-peptide were removed by blockade of HGF activity. This study identifies a novel role for HGF as an effector of C-peptide, possibly via an RA signaling pathway, highlighting C-peptide as a potential therapy for diabetic nephropathy.

Dataset Information

Citrullination of latency-associated peptide of TGF beta1

Publications

Extracellular citrullination inhibits the function of matrix associated TGF-β.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure