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| Content Provider | PubMed Central |
|---|---|
| Author | Ahamed, Jasimuddin Burg, Nathalie Yoshinaga, Keiji Janczak, Christin A. Rifkin, Daniel B. Coller, Barry S. |
| Copyright Year | 2008 |
| Abstract | Transforming growth factor-β1 (TGF-β1) has potent physiologic and pathologic effects on a variety of cell types at subnanomolar concentrations. Platelets contain 40 times as much TGF-β1 as other cells and secrete it as an inactive (latent) form in complex with latency-associated peptide (LAP), which is disulfide bonded via Cys33 to latent TGF-β binding protein 1 (LTBP-1). Little is known about how latent TGF-β1 becomes activated in vivo. Here we show that TGF-β1 released from platelets or fibroblasts undergoes dramatic activation when subjected to stirring or shear forces, providing a potential mechanism for physiologic control. Thiol-disulfide exchange appears to contribute to the process based on the effects of thiol-reactive reagents and differences in thiol labeling of TGF-β1 before and after stirring or shear. Activation required the presence of LTBP, as TGF-β1 contained in complex with only LAP could not be activated by stirring when studied as either a recombinant purified protein complex or in the platelet releasates or sera of mice engineered to contain an LAP C33S mutation. Release and activation of latent TGF-β1 in vivo was demonstrated in a mouse model 5 minutes after thrombus formation. These data potentially provide a novel mechanism for in vivo activation of TGF-β1. |
| Related Links | http://dx.doi.org/10.1182/blood-2008-04-151753 |
| Ending Page | 3660 |
| Page Count | 11 |
| Starting Page | 3650 |
| File Format | |
| ISSN | 00064971 |
| e-ISSN | 15280020 |
| Journal | Blood |
| Issue Number | 9 |
| Volume Number | 112 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2008-11-01 |
| Access Restriction | Open |
| Rights Holder | American Society of Hematology |
| Subject Keyword | Immunology Cell Biology Biochemistry Hematology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Hematology Biochemistry Immunology |
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