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Induction of transforming growth factor β1 by insulin‐like growth factor‐1 in dermal fibroblasts
Author(s) -
Ghahary Aziz,
Shen Qiong,
Shen You J.,
Scott Paul G.,
Tredget Edward E.
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199803)174:3<301::aid-jcp4>3.0.co;2-s
Subject(s) - transforming growth factor , growth factor , mink , insulin like growth factor , endocrinology , medicine , messenger rna , gene expression , biology , stimulation , cell culture , cell growth , growth inhibition , microbiology and biotechnology , chemistry , gene , biochemistry , receptor , ecology , genetics
Transforming growth factor β1 (TGF‐β1) belongs to a family of multifunctional modulatory proteins involved in cell growth, differentiation, development, and wound healing. Although the biological activities of TGF‐β1 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‐β1 by dermal fibroblasts and suggest a possible mechanism. An enzyme‐linked immunosorbent assay (ELISA) specific for TGF‐β 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‐β1 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‐β1 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‐β1 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‐β1 caused by IGF‐1 could be blocked by the addition of anti‐TGF‐β1 neutralizing antibody to the culture medium, suggesting that autoinduction of TGF‐β1 may be involved. An increase in IGF‐1‐induced TGF‐β1 should be important in many different physiological processes such as cellular proliferation, differentiation, and wound healing. These findings also suggest that induction of TGF‐β1 mRNA and protein by IGF‐1 may be a mechanism by which this cytokine is regulated in physiological and/or pathological conditions. J. Cell. Physiol. 174:301–309, 1998. © 1998 Wiley‐Liss, Inc.