4,911 research outputs found
Recommended from our members
AGAP2: modulating TGFβ1-signalling in the regulation of liver fibrosis
AGAP2 (Arf GAP with GTP-binding protein-like domain, Ankyrin repeat and PH domain 2) isoform 2 is a protein that belongs to the Arf GAP (GTPase activating protein) protein family. These proteins act as GTPase switches for Arfs, which are Ras superfamily members, being therefore involved in signaling regulation. Arf GAP proteins have been shown to participate in several cellular functions including membrane trafficking and actin cytoskeleton remodeling. AGAP2 is a multi-tasking Arf GAP that also presents GTPase activity and is involved in several signaling pathways related with apoptosis, cell survival, migration, and receptor trafficking. The increase of AGAP2 levels is associated with pathologies as cancer and fibrosis. Transforming growth factor beta-1 (TGF-β1) is the most potent pro-fibrotic cytokine identified to date, currently accepted as the principal mediator of the fibrotic response in liver, lung, and kidney. Recent literature has described that the expression of AGAP2 modulates some of the pro-fibrotic effects described for TGF-β1 in the liver. The present review is focused on the interrelated molecular effects between AGAP2 and TGFβ1 expression, presenting AGAP2 as a new player in the signaling of this pro-fibrotic cytokine, thereby contributing to the progression of hepatic fibrosis
Recommended from our members
Role of AGAP2 in the profibrogenic effects induced by TGFβ in LX-2 hepatic stellate cells
Liver damage induces hepatic stellate cells (HSC) activation, characterised by a fibrogenic, proliferative and migratory phenotype. Activated HSC are mainly regulated by transforming growth factor β 1 (TGFβ1), which increases the production of extracellular matrix proteins (e.g. collagen-I) promoting the progression of hepatic fibrosis. AGAP2 (ArfGAP with GTPase domain, ankyrin repeat and PH domain 2) is a GTPase/GTP-activating protein involved in the actin remodelling system and receptor recycling. In the present work the role of AGAP2 in human HSC in response to TGFβ1 was investigated. LX-2 HSC were transfected with AGAP2 siRNA and treated with TGFβ1. AGAP2 knockdown prevented to some extent the proliferative and migratory TGFβ1-induced capacities of LX-2 cells. An array focused on human fibrosis revealed that AGAP2 knockdown partially prevented TGFβ1-mediated gene expression of the fibrogenic genes ACTA2, COL1A2, EDN1, INHBE, LOX, PDGFB, TGFΒ12, while favored the expression of CXCR4, IL1A, MMP1, MMP3 and MMP9 genes. Furthermore, TGFβ1 induced AGAP2 promoter activation and its protein expression in LX-2. In addition, AGAP2 silencing affected TGFβ1-receptor 2 (TGFR2) trafficking in U2OS cells, blocking its effective recycling to the membrane. AGAP2 silencing in LX-2 cells prevented the TGFβ1-induced increase of collagen-I protein levels, while its over-expression enhanced collagen I protein expression in the presence or absence of the cytokine. AGAP2 overexpression also increased focal adhesion kinase (FAK) phosphorylated levels in LX-2 cells. FAK and MEK1 inhibitors prevented the increase of collagen-I expression caused by TGFβ1 in LX-2 overexpressing AGAP2. In summary, the present work shows for the first time, that AGAP2 is a potential new target involved in TGFβ1 signalling, contributing to the progression of hepatic fibrosis
Criteris per establir el contingut dels catàlegs de prestacions dels laboratoris clínics hospitalaris
Does HIV infection have an impact upon dental implant osseointegration? A systematic review
Background: A systematic review is made to determine whether human immunodeficiency virus (HIV) infection has an impact upon dental implant osseointegration. Material and Methods: A PubMed (MEDLINE) literature search was made of articles published up until 14 April 2014. The systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). The quality of the studies included in the review was assessed using the Methodological Index for Nonrandomized Studies (MINORS) and levels of evidence (based on the University of Oxford's Center for Evidence Based Medicine criteria). Results: The combinations of search terms resulted in a list of 132 titles. Nine studies finally met the inclusion criteria and were selected for inclusion in the systematic review. A total of 173 dental implants were placed in 80 patients (135 implants in 56 HIV-positive subjects and 38 implants in 24 HIV-negative patients), and a single loss of dental implant osseointegration was recorded in an HIV-positive patient. Conclusions: Our results suggest that dental implant placement in HIV-positive patients does not increase the dental implant failure rate. Prophylactic antibiotic treatment, the administration of highly active antiretroviral therapy, and control of the CD4+ T lymphocyte counts appear to be the main influencing factors in this respect. Given the few studies included in our systematic review, further prospective studies involving larger sample sizes and longer durations of follow-up are required in order to confirm the results obtained
Guia per a la verificació dels sistemes de mesura de magnituds biològiques ordinals per a l'acreditació segons la norma ISO 15189
- …