Molecular simulation and spectroscopic studies on the interaction between perfluorohexadecanoic acid and human serum albumin

In the present study, the interaction between Perfluorohexadecanoic acid (PFHxDA) and human serum albumin (HAS) was studied by fluorescence spectroscopy, molecular docking, dynamic simulation and circular dichroism (CD). The interaction character and the effect on human serum albumin conformation were measured by simulating the physiological condition (pH= 7.4). Experiments and simulation results revealed that PFHxDA molecules and HSA have regular fluorescence quenching, and the quenching mechanism is static quenching and non-radiative energy transfer. Thermodynamic analysis revealed the binding behavior was mainly governed by hydrophobic forces. Specific binding site experiments showed that the binding site of PFHxDA was a site I of HSA. The results from the CD spectrum demonstrated that PFHxDA changed the molecular conformation of HSA, which is consistent with the results obtained by molecular docking and dynamic simulation.

Semaphorin 4A enhances lung fibrosis through activation of Akt via PlexinD1 receptor.

Semaphorin 4A plays a regulatory role in immune function and angiogenesis. However, its specific involvement in controlling lung fibrosis, a process that is closely related to angiogenesis and inflammation is still poorly understood. In the present study, we show that treatment of Sema4A on normal lung fibroblasts induces expression of proteins that contribute to a contractile phenotype, including α-smooth muscle actin (α-SMA), ezrin, moesin, and paxillin. We confirm that Sema4A enhances the ability of lung fibroblasts to contract collagen gel. Sema4A treatment led to resistance to apoptosis in normal lung fibroblasts. Relative to normal lung fibroblasts, fibroblasts cultured from scars of patients with the fibrotic disease Systemic Sclerosis (SSc) showed elevated Sema4A secretion, enhanced α-SMA, ezrin, moesin, and paxillin expression, and high ability to induce collagen gel contraction. Using neutralizing antibody against Sema4A receptor, PlexinD1, we found that endogenous Sema4A signalling in SSc fibroblast was through PlexinD1 receptor. We then identified the signalling mechanism through which Sema4A-PlexinD1 promotes the ability of normal fibroblasts to contract a collagen gel matrix. Western blot analysis showed that Sema4A activated the Akt pathway in lung fibroblasts, and the specific inhibitor of Akt pathway, Akt inhibitor III, blocked the ability of Sema4A to promote the ability of lung fibroblasts to contract a collagen gel matrix. Thus, blocking Sema4APlexinD1- Akt cascades might be beneficial in reducing pulmonary fibrosis.