Effect of transforming growth factor beta on synthesis of glycosaminoglycans by human lung fibroblasts

Journal Article · Sat Sep 01 00:00:00 EDT 1990 · Experimental Lung Research; (USA)

DOI:https://doi.org/10.3109/01902149009068816· OSTI ID:6171880

Dubaybo, B A; Thet, L A ^[1]

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1. Veterans Administration Medical Center, Allen Park, MI (USA)

The processes of lung growth, injury, and repair are characterized by alterations in fibroblast synthesis and interstitial distribution of extracellular matrix components. Transforming growth factor beta (TGF-beta), which is postulated to play a role in modulating lung repair, alters the distribution of several matrix components such as collagen and fibronectin. We studied the effect of TGF-beta on the synthesis and distribution of the various glycosaminoglycans (GAGs) and whether these effects may explain its role in lung repair. Human diploid lung fibroblasts (IMR-90) were exposed to various concentrations of TGF-beta (0-5 nM) for variable periods of time (0-18 h). Newly synthesized GAGs were labeled with either (3H)glucosamine or (35S)sulfate. Individual GAGs were separated by size exclusion chromatography after serial enzymatic and chemical digestions and quantitated using scintillation counting. There was a dose-dependent increase in total GAG synthesis with maximal levels detected after 6 h of exposure. This increase was noted in all individual GAG types measured and was observed in both the cell associated GAGs (cell-matrix fraction) as well as the GAGs released into the medium (medium fraction). In the cell-matrix fraction, TGF-beta increased the proportion of heparan sulfate that was membrane bound as well as the proportion of dermatan sulfate in the intracellular compartment. In the medium fraction, TGF-beta increased the proportion of hyaluronic acid, chondroitin sulfate and dermatan sulfate released. We conclude that the role of TGF-beta in lung growth and repair may be related to increased synthesis of GAGs by human lung fibroblasts as well as alterations in the distribution of individual GAGs.

• OSTI ID: 6171880
• Journal Information: Experimental Lung Research; (USA), Vol. 16:5; ISSN 0190-2148
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
FIBROBLASTS
CELL DIVISION
GLYCOPROTEINS
BIOSYNTHESIS
GROWTH FACTORS
BIOLOGICAL FUNCTIONS
GLUCOSAMINE
LUNGS
MAN
SULFATES
SULFUR 35
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
EVEN-ODD NUCLEI
FUNCTIONS
HEXOSAMINES
HEXOSES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MITOGENS
MONOSACCHARIDES
NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PRIMATES
PROTEINS
RADIOISOTOPES
RESPIRATORY SYSTEM
SACCHARIDES
SOMATIC CELLS
SULFUR COMPOUNDS
SULFUR ISOTOPES
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques