Insulin‐like growth factor‐I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro

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Abstract
Connexin43 (cx43) forms gap junctions in astrocytes, and these gap junctions mediate intercellular communication by providing transport of low‐molecular‐weight metabolites and ions. We have recently shown that systemic growth hormone increases cx43 in the brain. One possibility was that local brain insulin‐like growth factor‐I (IGF‐I) could mediate the effect by acting directly on astrocytes. In the present study, we examined the effects of direct application of recombinant human IGF‐I (rhIGF‐I) on astrocytes in primary culture concerning cx43 protein expression and gap junctional communication (GJC). After 24 hr of stimulation with rhIGF‐I under serum‐free conditions, the GJC and cx43 protein were analyzed. Administration of 30 ng/ml rhIGF‐I increased the GJC and the abundance of cx43 protein. Cell proliferation of the astrocytes was not significantly increased by rhIGF‐I at this concentration. However, a higher concentration of rhIGF‐I (150 ng/ml) had no effect on GJC/cx43 but increased cell proliferation. Because of the important modulatory role of IGF binding proteins (IGFBPs) on IGF‐I action, we analyzed IGFBPs in conditioned media. In cultures with a low abundance of IGFBPs (especially IGFBP‐2), the GJC response to 30 ng/ml rhIGF‐I was 81%, compared with the average of 25%. Finally, as a control, insulin was given in equimolar concentrations. However, GJC was not affected, which suggests that rhIGF‐I acted via IGF‐I receptors. In summary, the data show that rhIGF‐I may increase GJC/cx43, whereas a higher concentration of rhIGF‐I—at which stimulation of proliferation occurred—did not affect GJC/cx43. Furthermore, IGFBP‐2 appeared to modulate the action of rhIGF‐I on GJC in astrocytes by a paracrine mechanism.
Funding Information
  • Swedish Medical Research Council (12X-12535, 21X-13015, 21X-11364)
  • Sahlgrenska universitetssjukhusets forskningsfonder
  • Kungliga Vetenskaps-och Vitterhetssamhället i Göteborg
  • Novo Nordisk Foundation
  • Åke Wiberg Foundation
  • Tore Nilsson's Foundation
  • Magnus Bergvall's Foundation
  • Karolinska Institute
  • Swedish Society of Medicine
  • Wera Ekström's Foundation
  • Swedish Freemasons' Foundation
  • Sällskapet Barnavård and Märta and Gunnar V. Philipson's Foundation

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