RGD Reference Report - Anti-latent TGF-beta binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells. - Rat Genome Database

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Anti-latent TGF-beta binding protein-1 antibody or synthetic oligopeptides inhibit extracellular matrix expression induced by stretch in cultured rat mesangial cells.

Authors: Hori, Y  Katoh, T  Hirakata, M  Joki, N  Kaname, S  Fukagawa, M  Okuda, T  Ohashi, H  Fujita, T  Miyazono, K  Kurokawa, K 
Citation: Hori Y, etal., Kidney Int. 1998 Jun;53(6):1616-25.
RGD ID: 10412058
Pubmed: PMID:9607192   (View Abstract at PubMed)
DOI: DOI:10.1046/j.1523-1755.1998.00908.x   (Journal Full-text)

Transforming growth factor-beta (TGF-beta) is usually secreted as a large latent complex associated with latent TGF-beta binding protein-1 (LTBP-1), which is known to bind to extracellular matrix (ECM) components. Although the LTBP-ECM interaction has been suggested to play a role in the activation and biological action of TGF-beta, the precise mechanism is still unclear. In glomerular hypertension mesangial cells are believed to perceive the increased cyclic strain and we have recently reported that cyclic mechanical stretch in vitro enhances the expression of ECM components via an autocrine/paracrine secretion of TGF-beta in cultured rat mesangial cells. Therefore, in this study we examined the role of LTBP-1 in the stretch-induced, TGF-beta-mediated ECM expression. Mesangial cells expressed mRNA for short and long forms of LTBP-1 (LTBP-1S and LTBP-1L, respectively). Mesangial cells were subjected to cyclic stretch to provide a maximal elongation of 20% at a rate of 60 cycles/min for 24 to 36 hours in the presence of polyclonal antibody raised against human LTBP-1 or synthetic oligopeptides corresponding to the N-terminal portions of human LTBP-1, which may work as competitive inhibitors against the LTBP-ECM association. Both anti-LTBP-1 antibody (Ab39) and synthetic oligopeptides inhibited the stretch-induced mRNA expression of type I collagen and fibronectin in a dose-dependent manner, but the inhibition by Ab39 or the oligopeptides was recovered by adding recombinant TGF-beta. Ab39 or the oligopeptides did not change the effect of exogenously added TGF-beta, such as growth-inhibition in mink lung epithelial cells. These results suggest that mesangial cells secrete TGF-beta as a large latent complex, and the LTBP-ECM interaction may be a pivotal step in TGF-beta action and ECM accumulation, providing a new therapeutic strategy against progression of glomerulosclerosis and other fibrotic diseases.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to mechanical stimulus  IEP 10412058 RGD 
positive regulation of collagen biosynthetic process  IMP 10412058 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ltbp1  (latent transforming growth factor beta binding protein 1)


Additional Information