Smooth muscle hypertrophy and the IGF-system
1996 (English)Doctoral thesis, comprehensive summary (Other academic)
Insulin-like growth factor-! (IGF-I) has both metabolic and mitogenic effects on smooth muscle cells (SMCs). The effects of IGF-I are modified by a group of binding proteins (IGFBPs). The present study was devoted to smooth muscle hypertrophy and the IGF-system in smooth muscle under different conditions.
In urinary bladder, smooth muscle hypertrophy, initiated by partial outletobstruction, was associated with a transient increase in IGF-I mRNA, and pronounced, sustained increases oflGFBP-2 and IGFBP-4 mRNA, as well as increased protein contents of IGF-I and IGFBP-2. Regression of smooth muscle hypertrophy was associated with normalization of levels ofiGF-I, IGFBP-2 and IGFBP-4 mRNA. Expression of the IGF-I receptor did not change significantly.
In portal vein, IGF-I mRNA and IGF-1 immunoreactivity were increased inhypertrophy induced by partialligation of the portal vein.
Abdominal coarctation caused a rapid hypertensive response accompanied by an increased wet weight of aortic media. This was coincident with a progressive increase in aortic IGFBP-2 mRNA, about 10-fold after 14 days.
The levels of IGFBP-4 mRNA in different muscle tissues and liver were decreased by diabetes and fasting, while IGFBP-2 mRNA was regulated in an organspecific 1nanner: with a sustained increase in liver and a decrease in aortic smooth muscle.
Smooth muscle hypertrophy also occured in the urinary bladder of diabetic rats. DNA synthesis was increased and peaked at 2 days after induction of diabetes. DNA content per bladder wet weight was decreased by 7 days. Initially there was no changes in IGF-I mRNA, while IGFBP-2 mRNA and protein in the bladders were increased and peaked by 7 days. IGFBP-4 mRNA increased only on day 7. The changes of mRNA in bladder differed from that in liver and aorta, and suggested an early effect of stretching of the bladder due to diuresis, and later a contribution by the diabetic state.
In cultured vascular SMCs, mechanical strain stimulated protein synthesis, but had little effect on DNA synthesis. However, mechanical strain potentiated the actions of IG:F'-1 and serum on both protein- and DNA synthesis, and influenced the effects of IGFBP-2.
In conclusion, development of smooth muscle hypertrophy is associated with specific changes in IGF-I, IGFBP-2 and IGFBP-4, suggesting that the IGF-system may play a role in this process.
Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 1996. , 69 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 500
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-25634Local ID: 10007ISBN: 91-7871-757-4OAI: oai:DiVA.org:liu-25634DiVA: diva2:246182
1996-06-03, Berzeliussalen, Hälsouniversitetet, Linköping, 09:00 (Swedish)
Clemmons, David R., Professor
Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.2009-10-082009-10-082012-07-17Bibliographically approved