Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI, USA.
Biomater Sci. 2021 Feb 9;9(3):645-652. doi: 10.1039/d0bm01374a.
Prolonged and elevated transforming growth factor-β1 (TGF-β1) signaling can lead to undesired scar formation during tissue repair and fibrosis that is often a result of chronic inflammation in the lung, kidney, liver, heart, skin, and joints. We report new TGF-β1 binding peptides that interfere with TGF-β1 binding to its cognate receptors and thus attenuate its biological activity. We identified TGF-β1 binding peptides from the TGF-β1 binding domains of TGF-β receptors and engineered their sequences to facilitate chemical conjugation to biomaterials using molecular docking simulations. The in vitro binding studies and cell-based assays showed that RIPΔ, which was derived from TGF-β type I receptor, bound TGF-β1 in a sequence-specific manner and reduced the biological activity of TGF-β1 when the peptide was presented either in soluble form or conjugated to a commonly used synthetic biomaterial. This approach may have implications for clinical applications such as treatment of various fibrotic diseases and soft tissue repair and offer a design strategy for peptide antibodies based on the biomimicry of ligand-receptor interactions.
转化生长因子-β1（TGF-β1）信号的持续和升高可导致组织修复过程中不理想的瘢痕形成和纤维化，这通常是肺部、肾脏、肝脏、心脏、皮肤和关节慢性炎症的结果。我们报告了新的 TGF-β1 结合肽，它们可以干扰 TGF-β1 与其同源受体的结合，从而减弱其生物学活性。我们从 TGF-β 受体的 TGF-β1 结合域中鉴定出 TGF-β1 结合肽，并对其序列进行了工程设计，以便使用分子对接模拟将其化学偶联到生物材料上。体外结合研究和基于细胞的测定表明，源自 TGF-β 型 I 受体的 RIPΔ 以序列特异性方式结合 TGF-β1，并且当肽以可溶性形式或与常用的合成生物材料偶联时，可降低 TGF-β1 的生物学活性。这种方法可能对各种纤维化疾病和软组织修复的临床应用具有重要意义，并为基于配体-受体相互作用的仿生肽抗体提供了一种设计策略。
