title: Growth factor PDGF-BB stimulates cultured cardiomyocytes to synthesize the extracellular matrix component hyaluronan.
abstract: BACKGROUND
  Hyaluronan (HA) is a glycosaminoglycan located in the interstitial space which is essential for both structural and cell regulatory functions in connective tissue. We have previously shown that HA synthesis is up-regulated in a rat model of experimental cardiac hypertrophy and that cardiac tissue utilizes two different HA synthases in the hypertrophic process. Cardiomyocytes and fibroblasts are two major cell types in heart tissue. The fibroblasts are known to produce HA, but it has been unclear if cardiomyocytes share the same feature, and whether or not the different HA synthases are activated in the different cell types.
  
  
  RESULTS
  This study shows, for the first time that cardiomyocytes can produce HA. Cardiomyocytes (HL-1) and fibroblasts (NIH 3T3) were cultivated in absence or presence of the growth factors FGF2, PDGF-BB and TGFB2. HA concentration was quantified by ELISA, and the size of HA was estimated using dynamic light scattering. Cardiomyocytes synthesized HA but only when stimulated by PDGF-BB, whereas fibroblasts synthesized HA without addition of growth factors as well as when stimulated by any of the three growth factors. When fibroblasts were stimulated by the growth factors, reverse dose dependence was observed, where the highest dose induced the least amount of HA. With the exception of TGFB2, a trend of reverse dose dependence of HA size was also observed.
  
  
  CONCLUSIONS
  Co-cultivation of cardiomyocytes and fibroblasts (80%/20%) increased HA concentration far more that can be explained by HA synthesis by the two cell types separately, revealing a crosstalk between cardiomyocytes and fibroblasts that induces HA synthesis. We conclude that dynamic changes of the myocardium, such as in cardiac hypertrophy, do not depend on the cardiomyocyte alone, but are achieved when both cardiomyocytes and fibroblasts are present.
authors.affiliation: Department of Public Health and Clinical Medicine/Medicine, Umeå University, Umeå, Sweden. urban.hellman@medbio.umu.se
authors.forename: Urban
authors.initials: U
authors.lastname: Hellman
authors.forename: Linus
authors.initials: L
authors.lastname: Malm
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Ma
authors.forename: Göran
authors.initials: G
authors.lastname: Larsson
authors.forename: Stellan
authors.initials: S
authors.lastname: Mörner
authors.forename: Michael
authors.initials: M
authors.lastname: Fu
authors.forename: Anna
authors.initials: A
authors.lastname: Engström-Laurent
authors.forename: Anders
authors.initials: A
authors.lastname: Waldenström
mesh_terms: D000818:Animals; D000077214:Becaplermin; D018920:Coculture Techniques; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; D014453:Glucuronosyltransferase / Q000378:metabolism*; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000166:cytology*; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012542:Scattering, Radiation
chemical_list: D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C491099:Has2 protein, mouse; D000076002:Hyaluronan Synthases