PMID- 9462692
OWN - NLM
STAT- MEDLINE
DCOM- 19980213
LR  - 20061115
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 174
IP  - 3
DP  - 1998 Mar
TI  - Induction of transforming growth factor beta 1 by insulin-like growth factor-1 in 
      dermal fibroblasts.
PG  - 301-9
AB  - Transforming growth factor beta1 (TGF-beta1) belongs to a family of 
      multifunctional modulatory proteins involved in cell growth, differentiation, 
      development, and wound healing. Although the biological activities of TGF-beta1 
      have been extensively studied, its regulation remains obscure. Here we report the 
      effects of insulin-like growth factor-1 (IGF-1) on the expression of TGF-beta1 by 
      dermal fibroblasts and suggest a possible mechanism. An enzyme-linked 
      immunosorbent assay (ELISA) specific for TGF-beta revealed a greater than twofold 
      increase (12.3 +/- 1.6 vs. 4.8 +/- 0.8 pg/10(4) cells, n = 7, P < 0.05) in the 
      protein in conditioned medium obtained from IGF-1-treated cells compared to that 
      from untreated controls. Similar results were obtained by the mink lung 
      epithelial cell growth inhibition assay. The results of Northern analysis 
      revealed a dose-dependent increase in TGF-beta1 mRNA in response to IGF-1 
      treatment. Using the optimum concentration of IGF-1 (100 ng/ml), a greater than 
      twofold increase (25.43 +/- 5.7 vs. 12.13 +/- 4.5, P < 0.05) in TGF-beta1 mRNA 
      was observed. This effect persisted for at least 48 h after IGF-1 was removed 
      from the culture medium. Nuclear run-on assay showed that this stimulation was 
      due, at least in part, to an increase in the rate of transcription of the 
      TGF-beta1 gene. Treatment of human dermal fibroblasts with IGF-1 caused a 
      substantial increase in c-fos and c-jun mRNA expression within 30 and 60 min, 
      respectively. In contrast to c-jun mRNA which was constitutively expressed by 
      dermal fibroblasts, the expression of c-fos mRNA was transient and only 
      detectable between 15 and 60 min. Greater than 58% of the increase in TGF-beta1 
      caused by IGF-1 could be blocked by the addition of anti-TGF-beta1 neutralizing 
      antibody to the culture medium, suggesting that autoinduction of TGF-beta1 may be 
      involved. An increase in IGF-1-induced TGF-beta1 should be important in many 
      different physiological processes such as cellular proliferation, 
      differentiation, and wound healing. These findings also suggest that induction of 
      TGF-beta1 mRNA and protein by IGF-1 may be a mechanism by which this cytokine is 
      regulated in physiological and/or pathological conditions.
FAU - Ghahary, A
AU  - Ghahary A
AD  - Department of Surgery, University of Alberta, Edmonton, Canada.
FAU - Shen, Q
AU  - Shen Q
FAU - Shen, Y J
AU  - Shen YJ
FAU - Scott, P G
AU  - Scott PG
FAU - Tredget, E E
AU  - Tredget EE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cells, Cultured
MH  - Culture Media, Conditioned
MH  - Fibroblasts/drug effects/metabolism
MH  - Genes, fos/drug effects
MH  - Genes, jun/drug effects
MH  - Humans
MH  - Insulin-Like Growth Factor I/*physiology
MH  - Lung/cytology
MH  - Mink
MH  - RNA, Messenger/biosynthesis
MH  - Skin/cytology/*metabolism
MH  - Transforming Growth Factor beta/*biosynthesis/drug effects
EDAT- 1998/02/14 05:48
MHDA- 2000/06/20 09:00
CRDT- 1998/02/14 05:48
PHST- 1998/02/14 05:48 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1998/02/14 05:48 [entrez]
AID - 10.1002/(SICI)1097-4652(199803)174:3<301::AID-JCP4>3.0.CO;2-S [pii]
AID - 10.1002/(SICI)1097-4652(199803)174:3<301::AID-JCP4>3.0.CO;2-S [doi]
PST - ppublish
SO  - J Cell Physiol. 1998 Mar;174(3):301-9. doi: 
      10.1002/(SICI)1097-4652(199803)174:3<301::AID-JCP4>3.0.CO;2-S.