Aim: Myofibroblasts play important roles in the pathogenesis of lung fibrosis. Transforming growth factor (TGF)‐β1 has been widely recognized as a key fibrogenic cytokine. The major signaling pathway of TGF‐β1 is through cytoplasmic Smad proteins. Our study investigated the role of individual TGF‐β1/Smad signal proteins in mediating α‐smooth muscle actin (α‐SMA) gene expression, which is a well‐known key marker of myofibroblast differentiation. Methods: We transiently cotransfected α‐SMA promoter‐luciferase fusion plasmid (p895‐Luc) and Smad expression plasmids and measured Luc activity in TGF‐β1‐treated human fetal lung fibroblasts. We induced Smad3 knockout mice lung fibrosis by bleomycin. α‐SMA protein expression was assessed by Western blotting. Collagen protein was analyzed by measuring hydroxyprolin. Myofibroblast morphology was assessed by immunohistochemistry. Results: We found that the overexpression of Smad3, not Smad2 markedly increased TGF‐β1‐induced α‐SMA promoter activity and α‐SMA protein expression in vitro, whereas the over‐expression of dominant negative mutant Smad3 and Smad7 repressed TGF‐β1 induced α‐SMA gene expression. Compared to wild‐type mice, Smad3 knockout mice showed attenuated lung fibrosis after bleomycin treatment, manifested by lower collagen production and myofibroblast differentiation. Conclusion: Our study suggested TGF‐β1/Smad3 is a major pathway which regulated the myofibroblast differentiation. This result indicates a potential significance for future attempts of attenuating the progression of human lung fibrosis by the inhibition of the Smad3 cascade.
Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.
CF in China is difficult to diagnose because of a combination of low awareness, atypical clinical symptoms, and a lack of sweat and genetic testing facilities in most hospitals. The mutations identified in Chinese CF patients are different from the common Caucasian gene mutations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.