Guo-Jun Yang

Matrix Metalloproteinases: A Review of Their Structure and Role in Systemic Sclerosis

Matrix metalloproteinases (MMPs) are the main enzymes involved in arterial wall extracellular matrix (ECM) degradation and remodeling, whose activity has been involved in various normal and pathologic processes, such as inflammation, fibrosis. As a result, the MMPs have come to consider as both therapeutic targets and diagnostic tools for the treatment and diagnosis of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Systemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by an excessive over-production of collagen and other ECM, resulting in skin thickening and fibrosis of internal organs. In recent years, abnormal expression of MMPs has been demonstrated with the pathogenesis of SSc, and the association of different polymorphisms on MMPs genes with SSc has been extensively studied. This review describes the structure, function and regulation of MMPs and shortly summarizes current understanding on experimental findings, genetic associations of MMPs in SSc.

MicroRNA-29: a potential therapeutic target for systemic sclerosis.

Introduction: Systemic sclerosis (SSc) is a systemic autoimmune disease of unknown cause characterized by microvasculopathy, fibroblast activation, and excessive production of collagen, causing tissue and organ damage. Effective medical treatment for SSc is lacking because the etiology and pathogenesis of SSc are not fully understood. MicroRNAs (miRNAs) are endogenous, regulatory, single-stranded, noncoding RNAs that negatively modulate gene expression by either promoting the degradation of mRNA or down-regulating the protein production by translational repression. Among them, miRNA-29 is recently discovered as a class of miRNAs which is related to fibrotic disease. Numerous evidences have confirmed that miRNA-29 involved in the expression of extracellular matrix (ECM) and regulated organ fibrosis. These findings revealed a potential and appealing role for miRNA-29 as SSc therapeutic targets. Areas covered: This review provides a comprehensive view on the biogenesis and functions of miRNAs. We also discuss the aberrant expression of miRNA-29 in SSc, and summarize current understanding of miRNA-29 involved in the process of fibrosis. Finally, we discuss the therapeutic potential of targeting miRNA-29 in SSc. Expert opinion: Although the exact pathogenesis of SSc still remains to be clarified, Targeting miRNA-29 may serve as a promising therapy strategy.

The risk of cancer development in systemic sclerosis: A meta-analysis

OBJECTIVES Systemic sclerosis is a multi-system disorder of connective tissue characterized by Raynauds phenomenon and fibrosis of various organs. The risk of development of cancer in systemic sclerosis (SSc) has been extensively investigated with inconclusive results. To shed some light on the controversy, we conducted a meta-analysis of all published articles linking SSc to the risk of cancer development. METHODS Relevant electronic databases were searched for English-language studies characterizing the association of cancers in patients with SSc. Standardized incidence rate (SIR) with its 95% confidence interval (CI) of each study was combined using a fixed/random effect model. RESULTS A total of seven papers including 7183 SSc patients were identified, of which 7 reported the SIR for lung cancer, 4 for non-Hodgkins lymphoma (NHL) and 4 for hematopoietic cancer and 7 for breast cancer. Compared with the general population, the combined SIR was 3.14 (95% CI: 2.02-4.89), 2.68 (95% CI: 1.58-4.56), 2.57 (95% CI: 1.79-3.68) and 1.09 (95% CI: 0.86-1.38), respectively. Significant heterogeneity was observed in lung cancer group (Q=26.13, P<0.001, I(2)=77%). Potential publication bias was absent. CONCLUSIONS This present meta-analysis demonstrated an increased risk of lung, non-Hodgkins lymphoma and hematopoietic cancers among patients with SSc, but not for breast cancer. However, some of the available data were several decades old, and future studies taking new treatment strategies into account are required.

Therapeutic potential of interleukin-17 in inflammation and autoimmune diseases

Introduction: Interleukin-17 (IL-17) is a proinflammatory cytokine that mainly produced by T helper 17 (Th17) cells. In this article, we discussed the role of IL-17 in inflammation and autoimmune diseases, and the therapeutic strategies targeting IL-17. Areas covered: In this article, we discussed the proinflammatory cytokine IL-17 and IL-17 receptors signals, and their regulation. IL-17 expression was abnormal in the bacterium, virus and fungus infection, and its higher level caused the tissue inflammation. IL-17 was involved in the pathological process of autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematosus, and IL-17 has been put as a therapeutic target in the clinic. Expert opinion: IL-17/IL-17R signals and their application in inflammation process still need to be explored. Therapeutic strategies targeting IL-17 in autoimmune diseases ameliorated the inadequate response to anti-TNF-α therapy.

Association of interleukin 1 family with systemic sclerosis.

Systemic sclerosis is a connective tissue disease characterized with fibrosis of skin and/or internal organs, and its specific pathological mechanism remains incompletely understood. IL-1 family, whose biological properties are typically pro-inflammatory and pro-fibrosis, has been associated with systemic sclerosis (SSc). Interleukin (IL)-1 family has 11 members, IL-1α, IL-1β, IL-1Ra, IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-37, and IL-38. With the exception of IL-1Ra and IL-36Ra, each member has its own receptor signal. Abnormal expression of IL-1 and its potential role in the fibrosis process have been probed earliest, as well as its gene polymorphisms with SSc. IL-33 and IL-18 have also been discussed in the recent years, and IL-33 may contribute to the fibrosis of SSc, while IL-18 remains to be researched to confirm its role in fibrosis process. There is a lack of studies on the association of the other members of the IL-1 family, which might provide us the future study area; much more efforts need to be put on this matter.

The Influence of Different Solvents on Systemic Sclerosis: An Updated Meta-analysis of 14 Case-Control Studies.

BackgroundSeveral studies have collected detailed data to examine which specific solvents account for the association between solvents and risk of systemic sclerosis (SSc). These studies generally reported elevated risks associated with many of the specific solvents examined, such as toluene, xylene, and trichloroethylene. The previous meta-analysis was not able to conduct separate analyses for specific solvent subtypes. ObjectiveThe aims of the new meta-analysis were to investigate a more comprehensive estimate and to consider the effect of different solvents on SSc. MethodsWe searched PubMed, Biosis Previews, China National Knowledge Infrastructure, and Wanfang for all articles published before July 2015. Fourteen case-control studies (1657 patients and 3838 controls) were included. The quality of studies was scored according to the Newcastle-Ottawa scale. The final odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a fixed- or random-effects model according to heterogeneity test. Publication bias was assessed using Begg test. ResultsThe risk of SSc was significantly different among sex, age, and exposure assessment methods. Separate analyses for specific solvent subtypes indicated that SSc was associated with aromatic solvents (OR, 2.72; 95% CI, 1.21–6.09), trichloroethylene (OR, 2.07; 95% CI, 1.34–3.17), halogenated solvents (OR, 1.49; 95% CI, 1.12–1.99), and ketones (OR, 4.20; 95% CI, 2.19–8.06). ConclusionsExposure to identified types solvents does seem to be a risk factor for developing SSc. Needed efforts to decrease such exposures are discussed.

The association between vibration and vascular injury in rheumatic diseases: A review of the literature

Abstract Vascular manifestations can be seen early in the pathogenesis of inflammatory rheumatic diseases. Animal experiments, laboratory and clinical findings indicated that acute or long-term vibration exposure can induce vascular abnormalities. Recent years, in addition to Raynauds phenomenon (RP), vibration as a risk factor for other rheumatic diseases has also received corresponding considered. This review is concentrated upon the role of vibration in the disease of systemic sclerosis (SSc). In this review, we are going to discuss the main mechanisms which are thought to be important in pathophysiology of vascular injury under the three broad headings of “vascular”, “neural” and “intravascular”. Aspects on the vibration and vascular inflammation are briefly discussed. And the epidemiological studies related to vibration studies in SSc and other rheumatic diseases are taken into account.