The Developmentally Regulated Avian Ch21 Lipocalin Is an Extracellular Fatty Acid-binding Protein

Cancedda, Fiorella Descalzi; Malpeli, Mara; Gentili, Chiara; Marzo, Vincenzo Di; Bet, Paola; Carlevaro, Mariella F.; Cermelli, Silvia; Cancedda, Ranieri

doi:10.1074/jbc.271.33.20163

Cited by 41 publications

(43 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular we reported that Ex-FABP, an extracellular lipocalin that specifically binds unsaturated long chain fatty acids, avidin, a biotin binding protein, and ovotransferrin, an iron binding protein, were constitutively (''physiologically'') expressed in differentiated chondrocytes, and strongly overinduced by stimulation of the same cells with inflammatory agents such as LPS and inflammatory cytokines [Cancedda et al, 1990;Gentili et al, 1994;Cancedda et al, 1996;Zerega et al, 2001]. Serum Amyloid A mRNA was also highly expressed in hyperthrophic cells.…”

mentioning

confidence: 99%

p38/NF‐kB‐dependent expression of COX‐2 during differentiation and inflammatory response of chondrocytes

Ulivi

Giannoni

Gentili

et al. 2008

J of Cellular Biochemistry

Self Cite

131

View full text Add to dashboard Cite

Studying cartilage differentiation, we observed the emergence of inflammation-related proteins suggesting that a common pathway was activated in cartilage differentiation and inflammation. In the present paper, we investigated the expression pathway of the inflammation-related enzyme Cyclooxygenase-2 (COX-2) during differentiation and inflammatory response of the chondrocytic cell line MC615. Cells were cultured either as (i) proliferating prechondrogenic cells expressing type I collagen or (ii) differentiated hyperconfluent cells expressing Sox9 and type II collagen. The p38 and the NF-kB pathways were investigated in standard conditions and after inflammatory agents treatment. NF-kB was constitutively activated in differentiated cells. The activation level of NF-kB in differentiated cells was comparable to the level in proliferating cells treated with the inflammatory agent LPS. In both cases, p65 was bound to the NF-kB consensus sequence of COX-2 promoter. p38, constitutively activated in differentiated cells, was activated in proliferating cells by treatment with LPS or IL-1alpha. In stimulated proliferating cells the two pathways are connected since addition of the p38-specific inhibitor SB203580 inhibited p38 activation, significantly reduced NF-kB activation and repressed COX-2 synthesis indicating that p38 is upstream NF-kB activation and COX-2 synthesis. In differentiated cells, the treatment with the inflammatory agent neither enhance NF-kB activation, nor synthesis of COX-2 while the addition of SB203580 neither repressed activation of p38, nor COX-2 synthesis, suggesting a constitutive activation of a p38/NF-kB/COX2 pathway. Our data indicate that in chondrocytes, COX-2 is expressed via p38 activation/NF-kB recruitment during both differentiation and inflammatory response.

show abstract

mentioning

confidence: 99%

p38/NF‐kB‐dependent expression of COX‐2 during differentiation and inflammatory response of chondrocytes

Ulivi

Giannoni

Gentili

et al. 2008

J of Cellular Biochemistry

Self Cite

131

View full text Add to dashboard Cite

show abstract

“…196: 464-473, 2003. We have reported that Ex-FABP, a lipocalin selectively binding fatty acids (Descalzi Cancedda et al, 1996), is expressed in developing embryonic hypertrophic cartilage (Descalzi Cancedda et al, 1988), in granulocytes (Dozin et al, 1992), in newly formed muscle fibres, and in developing heart myocardium (Gentili et al, 1998). Inflammatory agents, such as bacterial endotoxin lipopolysaccharide (LPS) and interleukin 6 (IL-6) dramatically enhance ex-FABP expression, in differentiating hypertrophic chondrocytes, and forming myotubes during standard cell culture condition (Cermelli et al, 2000).…”

mentioning

confidence: 99%

Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting

Marco

Sessarego

Zerega

et al. 2003

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

Ex-FABP, an extracellular fatty acid binding lipocalin, is physiologically expressed by differentiating chicken chondrocytes and myoblasts. Its expression is enhanced after cell treatment with inflammatory stimuli and repressed by anti-inflammatory agents, behaving as an acute phase protein. Chicken liver fragments in culture show enhanced protein expression after bacterial endotoxin treatment. To investigate the biological role of Ex-FABP, we stably transfected proliferating chondrocytes with an expression vector carrying antisense oriented Ex-FABP cDNA. We observed a dramatic loss of cell viability and a strong inhibition of cell proliferation and differentiation. When chondrocytes were transfected with the antisense oriented Ex-FABP cDNA we observed that Ex-FABP down-modulation increased apoptotic cell number. Myoblasts transfected with the same expression vector showed extensive cell death and impaired myotube formation. We suggest that Ex-FABP acts as a constitutive survival protein and that its expression and activation are fundamental to protect chondrocytes from cell death.

show abstract

“…The most abundant of these quiescence-specific proteins is a member of the lipocalin family of lipid-binding proteins, designated p20K, chicken p21, or extracellular fatty acid-binding protein (EX-FABP) (13,14). Maximal expression of p20K is observed in contact-inhibited CEF and in chicken heart mesenchymal cells rendered quiescent by culture in plasma-containing rather than serum-containing medium (12).…”

mentioning

confidence: 97%

“…For instance, C/EBP␤ is widely expressed in quiescent hepatocytes and is capable of inhibiting the proliferation of hepatoma cells, but mice nullizygous for C/EBP␤ have impaired liver regeneration following partial hepatectomy (35)(36)(37). Likewise, C/EBP␤ is expressed in the mammary epithelium, which is composed -12), or Fra2 (lanes [13][14][15][16]. Confluence (RCASBP) or maximal cell density (c-Jun, JunD, Fra-2) was reached at day 2 in this experiment.…”

Section: C/ebp␤ Is a Negative Regulator Of Fibroblast Proliferation-mentioning

confidence: 99%

Opposing Roles of C/EBPβ and AP-1 in the Control of Fibroblast Proliferation and Growth Arrest-specific Gene Expression

Gagliardi

Maynard

Miyake

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Chicken embryo fibroblasts (CEF) express several growth arrest-specific (GAS) gene products in G 0 . In contact-inhibited cells, the expression of the most abundant of these proteins, the p20K lipocalin, is activated at the transcriptional level by C/EBP␤. In this report, we describe the role of C/EBP␤ in CEF proliferation. We show that the expression of a dominant negative mutant of C/EBP␤ (designated ⌬184-C/EBP␤) completely inhibited p20K expression at confluence and stimulated the proliferation of CEF without inducing transformation. Mouse embryo fibroblasts nullizygous for C/EBP␤ had a proliferative advantage over cells with one or two functional copies of this gene. C/EBP inhibition enhanced the expression of the three major components of AP-1 in cycling CEF, namely c-Jun, JunD, and Fra-2, and stimulated AP-1 activity. In contrast, the over-expression of C/EBP␤ caused a dramatic reduction in the levels of AP-1 proteins. Therefore, C/EBP␤ is a negative regulator of AP-1 expression and activity in CEF. The expression of cyclin D1 and cell proliferation were stimulated by the dominant negative mutant of C/EBP␤ but not in the presence of TAM67, a dominant negative mutant of cJun and AP-1. CEF over-expressing c-Jun, and to a lesser extent JunD and Fra-2, did not growth arrest at high cell density and did not express p20K. Therefore, AP-1 interfered with the action of C/EBP␤ at high cell density, indicating that these factors play opposing roles in the control of GAS gene expression and CEF proliferation.

show abstract

The Developmentally Regulated Avian Ch21 Lipocalin Is an Extracellular Fatty Acid-binding Protein

Cited by 41 publications

References 46 publications

p38/NF‐kB‐dependent expression of COX‐2 during differentiation and inflammatory response of chondrocytes

p38/NF‐kB‐dependent expression of COX‐2 during differentiation and inflammatory response of chondrocytes

Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting

Opposing Roles of C/EBPβ and AP-1 in the Control of Fibroblast Proliferation and Growth Arrest-specific Gene Expression

Contact Info

Product

Resources

About