Anti-MMP-1 monoclonal antibody, clone TC13f

Early pulmonary fibrosis after acute lung injury leads to poor prognosis and high mortality. Pterostilbene (Pts), a bioactive component in blueberries, possesses anti-inflammatory, antioxidative and antifibrotic properties. However, the effects of Pts on lipopolysaccharide (LPS)-induced pulmonary fibrosis are still unknown. In our study, the Pts group showed lower lung injury and fibrosis scores, and lower levels of hydroxyproline and protein (collagen I and transforming growth factor-beta) than the scores and levels in mice treated with LPS. MMP-1 was the degrading enzyme of collagen I and LPS caused the inhibition of MMP-1, disturbing the degradation of collagen. Additionally, Pts remarkably reversed the LPS-induced inhibition of interleukin-10 and the release of tumor necrosis factor-alpha, interleukin-6 and interleukin-1 beta. In terms of cellular pathways, Pts treatment ameliorated LPS-activated nuclear factor kappa B (NF-kappa B) and NOD-like receptor NLRP3 signaling. Besides, LPS-induced low levels of A20 could be activated by Pts. In addition, Pts treatment reversed the high levels of Caspase-3, poly ADP-ribose polymerase (PARP) and Bcl2-associated X protein (Bax) expression and the low levels of B cell lymphoma/lewkmia-2 (Bcl2) that had been induced by LPS. Moreover, oxidative stress is also involved in the pathogenesis of fibrosis. Our findings indicate that LPS injection triggered the production of myeloperoxidase (MPO) and malondialdehyde (MDA) and the depletion of superoxide dismutase (SOD) and glutathione (GSH), and that these effects were notably reversed by treatment with Pts. In addition, Pts induced the dissociation of Kelch-like epichlorohydrin-associated protein-1 (Keap-1) and NF-E2 related factor-2 (Nrf2) and the activation of downstream genes (heme oxygenase-1, NAD(P)H:quinine oxidoreductase, glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modifier). In conclusion, oxidative stress, apoptosis and inflammation are involved in early pulmonary fibrosis and Pts exerts a protective effect by activating Keap-1/Nrf2, inhibiting caspase-dependent A20/NF-kappa B and NLRP3 signaling pathways.

Background Platelet-rich plasma (PRP) is a blood fraction that contains high concentrations of several growth factors. PRP has been recently used in skin wound healing and rejuvenation. However, the precise molecular mechanisms underlying PRP-induced wound healing are unknown. Aims This study aimed to evaluate the effects of PRP on extracellular matrix remodeling, which requires the activation of dermal fibroblasts. Methods Cell proliferation and migration assay, enzyme-linked immunosorbent analysis, and Western blotting were performed on PRP-treated human skin fibroblasts. Results Platelet numbers were enhanced by 4.6-fold in PRP compared to that in whole blood. PRP stimulated the proliferation and migration of human dermal fibroblasts and increased the expression of human procollagen I alpha 1, elastin, MMP-1, and MMP-2 in human dermal fibroblasts. PRP-treated human dermal fibroblasts also showed a dramatic reduction in the phosphorylation of c-Jun N-terminal kinase (JNK), whereas total JNK levels were not significantly reduced. Conclusions Collectively, PRP induced increased expression of type I collagen, elastin, MMP-1, and MMP-2, thereby accelerating wound healing. Our findings reveal basic mechanisms underlying PRP-mediated tissue remodeling. Thus, these results could be exploited for clinical dermatology and skin rejuvenation.