Rabbit Anti-Human SMAD3 (internal) Polyclonal antibody

Patients with late-onset asthma (LOA) have poor clinical outcomes. Osteopontin (OPN) is associated with airway inflammation and remodeling. To investigate the role of OPN in LOA compared to early-onset asthma (EOA), serum OPN levels were compared between 131 adult asthma patients (48 LOA and 83 EOA patients) and 226 healthy controls (HCs). BALB/c mice were sensitized with ovalbumin with/without polyinosinic-polycytidylic acid (poly(I:C)) from week 6 (A6 mice) or week 12 (A12 mice) after birth. Airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF), cell counts, histology, and Spp1 expression were assessed. The levels of OPN, transforming growth factor beta 1 (TGF-beta 1), chitinase 3-like 1 (CH3L1), and interleukin (IL) 5 were measured by ELISA. The expression of Smad3 phosphorylation and tissue transglutaminase 2 (TGM2) was evaluated by Western blot. The serum OPN levels were significantly higher in asthma patients than in HCs and in LOA patients than in those with EOA (P < 0.05) and were positively correlated with serum TGF-beta 1 and CH3L1 (r = 0.174, r = 0.264; P < 0.05). A12 mice showed elevated AHR with increased levels of OPN/TGF-beta 1/IL-5 in BALF and Spp1 compared to A6 mice. Poly(I:C) induced remarkable TGF-beta 1, CH3L1, Th2 cytokine, and OPN levels in BALF and the expression of phosphorylated Smad3, TGM2, and Spp1 in the lungs. OPN triggered TGF-beta 1/Smad3 signaling in the lungs, which was suppressed by dexamethasone and anti-IL5 antibody. In conclusion, aging and exposure to viral infections may induce OPN release and consequently modulate inflammation and TGF-beta 1/Smad3-related remodeling, contributing to the development of LOA. Asthma: Inflammatory protein drives adult-onset disease Aging and viral infections in older individuals may combine to spur the release of an inflammatory protein implicated in late-onset asthma. A team led by Hae-Sim Park from Ajou University School of Medicine, Suwon, South Korea, showed that people who develop asthma after age 40 have higher blood levels of osteopontin, a multifunctional protein with roles in airway inflammation and tissue remodeling, than people who develop asthma at a younger age or healthy individuals. The researchers developed two ovalbumin-induced asthma models in younger and older mice, and found that older mice developed more severe airway hyperresponsiveness with higher levels of osteopontin, among other inflammatory markers, which were emnhanced by viral infection. Drug therapies that target osteopontin signaling could help combat the late-onset asthma.

Posterior capsule opacification (PCO) as a result of proliferation and fibrogenesis of lens epithelial cells (LECs) is the most frequent long-term complication of modern cataract surgery. LECs may undergo epithelial-mesenchymal transition (EMT) that resembles the morphological and molecular characteristics of PCO. A pre-identified novel, hepatocyte growth factor (HGF)-derived peptide H-RN, was reported to exhibit anti-angiogenic activity and anti-inflammatory effects in ocular cells bothin vitroandin vivo. However, the role of H-RN in the promotion of the development of EMT in LECs is unknown. In the present study, the effects of H-RN on the development of EMT induced by transforming growth factor (TGF)-beta in human LECs, and the possible signaling pathways participating in this process were investigated. The results showed that H-RN promoted the expression of the EMT-associated markers, alpha-smooth muscle actin and fibronectin, whereas the expression of E-cadherin and connexin 43 were reduced. The morphological changes typically associated with EMT seen in LECs induced by TGF-beta 2 were inhibited by H-RN, which was consistent with the effects of a TGF-beta 2 inhibitor, SB431542. Smad2 and Smad3 phosphorylation induced by TGF-beta 2 were reduced by H-RN, and phosphorylation of Akt, mTOR and P70S6K induced by TGF-beta 2 were also notably reduced by H-RN in LECs. Therefore, the results of the present study showed that H-RN treatment significantly suppressed the development of EMT induced by TGF-beta 2, at least partially through the TGF-beta/Smad and Akt/mTOR signaling pathways in human LECs. The present study highlights that H-RN, a novel HGF-derived peptide, may be a novel therapeutic agent for prevention and treatment of PCO.