| Autor: |
Reed, NI, Jo, H, Chen, C, Tsujino, K, Arnold, TD, DeGrado, WF, Sheppard, D |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Zdroj: |
Reed, NI; Jo, H; Chen, C; Tsujino, K; Arnold, TD; DeGrado, WF; et al.(2015). The αvβ1integrin plays a critical in vivo role in tissue fibrosis. Science Translational Medicine, 7(288). doi: 10.1126/scitranslmed.aaa5094. UCSF: Retrieved from: http://www.escholarship.org/uc/item/5vh192c4 |
| DOI: |
10.1126/scitranslmed.aaa5094. |
| Popis: |
Integrins are transmembrane heterodimeric receptors that contribute to diverse biological functions and play critical roles in many human diseases. Studies using integrin subunit knockout mice and inhibitory antibodies have identified important roles for nearly every integrin heterodimer and led to the development of a number of potentially useful therapeutics. One notable exception is the αvβ1integrin. αvand β1subunits are individually present in numerous dimer pairs, making it challenging to infer specific roles for αvβ1by genetic inactivation of individual subunits, and αvβ1complex-specific blocking antibodies do not yet exist. We therefore developed a potent and highly specific small-molecule inhibitor of αvβ1to probe the function of this understudied integrin. We found that αvβ1, which is highly expressed on activated fibroblasts, directly binds to the latency-associated peptide of transforming growth factor-β1(TGFβ1) and mediates TGFb1 activation. Therapeutic delivery of this αvβ1inhibitor attenuated bleomycin-induced pulmonary fibrosis and carbon tetrachloride-induced liver fibrosis, suggesting that drugs based on this lead compound could be broadly useful for treatment of diseases characterized by excessive tissue fibrosis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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