ARC expression leads to decreased TGF-b activity. Last, SPARC may activate nuclear localization of b-catenin and integrin-linked kinase. The activation of b-catenin in fibroblasts promotes stabilization of the myofibroblast phenotype and an anti-apoptotic phenotype, while the activation of ILK leads to ROS production, one of the causative Folic acid factors of recurrent epithelial damage in fibrotic lungs. Several mouse models have confirmed that SPARC is affiliated with pulmonary fibrosis. Savani et al. used bleomycin sulfate infused intra-tracheally at 0.15 U/mouse to cause a fibrotic response in WT and SPARC-null mice. The outcome revealed that SPARC-null mice had increased tissue destruction and increased inflammatory cell recruitment, specifically neutrophils, in comparison to bleomycin-treated WT mice. These findings were consistent with Sangaletti’s study. The reasons behind the outcome are not Pancuronium dibromide readily apparent, but SPARC could be produced by both bone marrow-derived and lung fibroblasts, and different sources might play a different role. Sangaletti used bone marrow chimeric mice and found that expression of SPARC in pulmonary fibroblasts promoted collagen deposition, while the expression of SPARC in bone marrow cells impeded inflammatory infiltrates. This elaborate study demonstrated the intricate association between fibrosis and inflammation. It is well known that genetic and environmental factors are involved in the development of CWP. To our knowledge, this is the first evaluation of the association between functional SNPs in SPARC and pneumoconiosis susceptibility in a Chinese population. Statistical analyses identified three SNPs that were significantly associated with pneumoconiosis. In addition, the rs1059279 was not included in 1000 Genome database when we search for LD in SNP selection process. However, we found rs1059279 was in high linkage disequilibrium with rs1053411 using our own genotyped data. Furthermore, stratification analyses were applied and hinted that each of these three SNPs significantly increased CWP risk of individuals with 0-20 pack-years smoking. Furthermore, we speculate on the function of three SNPs: rs1053411 might affect the miRNA-LOSS of hsa-miR-4311, while rs1059829 might affect the miRNA-LOSS of hsa-miR-541-5p, which could well be involved in the regulation of mRNA production and stability. Moreover, rs1059829 was a locus of expression for Quantitative Trait Loci and Transcription Factor Binding Site, thus could affect transcription activity and even consequently predispose individuals to excessive fibrogenesis. The relevant TFBS include Nfkb1, Interferon regulatory factor 4, B-cell CLL/lymphoma 3, and so on, all of which have innumerable links to the molecular mechanisms that result in the transcriptional activation of genes responsible for the fibrotic process. These findings set new insights into the role of SPARC in the pathogenesis of pneumoconiosis. Several limitations of this study should be addressed. First, the possibility of selection bias of subjects could not be ruled out in this population-based, case-control study. Second, our sample size was only moderate, further studies are required to replicate our results in larger and more diverse ethnic populations. Third, since five SNPs were tested, one might apply an appropriate multiple testing correction, such as the Bonferroni correction, otherwise the significant association between these three SNPs and CWP risk should be interpreted with caution.