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ALK5 inhibition blocks TGFβ-induced CCN1 expression in human foreskin fibroblasts |
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| Authors: | Katherine Thompson Hannah Murphy-Marshman Andrew Leask |
| Institution: | 1. Department of Dentistry, University of Western Ontario, London, ON, Canada, N6A 5C1 2. Department of Biology, University of Western Ontario, London, ON, Canada, N6A 5C1 3. Department of Biochemistry, University of Western Ontario, London, ON, Canada, N6A 5C1 4. Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Dental Sciences Building, University of Western Ontario, London, ON, Canada, N6A 5C1 |
| Abstract: | The potent profibrotic cytokine TGFβ induces connective tissue growth factor (CCN2/CTGF) is induced in fibroblasts in a fashion sensitive to SB-431542, a specific pharmacological inhibitor of TGFβ type I receptor (ALK5). In several cell types, TGFβ induces CCN1 but suppresses CCN3, which opposes CCN1/CCN2 activities. However, whether SB-431542 alters TGFβ-induced CCN1 or CCN3 in human foreskin fibroblasts in unclear. Here we show that TGFβ induces CCN1 but suppresses CCN3 expression in human foreskin fibroblasts in a SB-431542-sensitive fashion. These results emphasize that CCN1/CCN2 and CCN3 are reciprocally regulated and support the notion that blocking ALK5 or addition of CCN3 may be useful anti-fibrotic approaches. |
| Keywords: | Fibroblasts CCN1 CCN2 cyr61 ctgf TGFbeta ALK5 |
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