Dataset Information

PTMA, a new identified autoantigen for oral submucous fibrosis, regulates oral submucous fibroblast proliferation and extracellular matrix.

ABSTRACT: Oral submucous fibrosis (OSF) is a chronic, insidious disease. The presence of autoantibodies in sera of OSF patients is the most characteristic and direct evidence of OSF being an autoimmune disease. To identify the specific autoantigens which could contribute to antibody production, the Human Proteome Microarrays composed of 19000 full-length unique proteins were employed. 45 proteins correlated with OSF were identified. To validate these results, we used ELISA to validate 28 OSF-associated autoantigens in extended samples. 8 autoantigens were positive in OSF serum with high frequency compared to the healthy controls. Moreover, the mRNA expression of 8 candidates was up-regulated in OSF oral submucous tissues; among them, the protein level of PTMA, the one with the highest positive frequency, was also increased. Through searching the Bioinformatics Public Database and performing the Spearman's rank correlation analysis, we observed that PTMA was positively correlated with fibrosis-related TGF?1 and SMAD4, the downstream gene of TGF?1. In TGF?1-induced fibrosis model of primary human oral submucous fibroblast, PTMA knockdown reversed TGF?1-induced fibrosis process through inhibiting the cell viability and proliferation of fibroblast, reducing the protein levels of PTMA, Collagen I, ?-SMA and MMP9 and increasing the protein levels of SMAD4. In contrast, PTMA overexpression enhanced TGF?1-induced fibrosis process. Taken together, PTMA is involved in TGF?1-induced fibrosis in the primary human submucous fibroblast by regulating the expression of ECM-related markers and the downstream genes of TGF?1. In conclusion, PTMA presents an essential autoantigen during OSF process; targeting PTMA might be a promising strategy for OSF treatment.

SUBMITTER: Wang J

PROVIDER: S-EPMC5650380 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

PTMA, a new identified autoantigen for oral submucous fibrosis, regulates oral submucous fibroblast proliferation and extracellular matrix.

Wang Jie J You Jialing J Wang Lekai L Wang Huimin H Tian Tian T Wang Wenjin W Jia Lina L Jiang Canhua C

Oncotarget 20170824 43

Oral submucous fibrosis (OSF) is a chronic, insidious disease. The presence of autoantibodies in sera of OSF patients is the most characteristic and direct evidence of OSF being an autoimmune disease. To identify the specific autoantigens which could contribute to antibody production, the Human Proteome Microarrays composed of 19000 full-length unique proteins were employed. 45 proteins correlated with OSF were identified. To validate these results, we used ELISA to validate 28 OSF-associated au ...[more]

PMID: 29088825

Similar Datasets

Project description:Maintaining a balanced state in remodeling the extracellular matrix is crucial for tissue homeostasis, and this process is altered during skin cancer progression. In melanoma, several proteolytic enzymes are expressed in a time and compartmentalized manner to support tumor progression by generating a permissive environment. One of these proteases is the matrix metalloproteinase 14 (MMP14). We could previously show that deletion of MMP14 in dermal fibroblasts results in the generation of a fibrotic-like skin in which melanoma growth is impaired. That was primarily due to collagen I accumulation due to lack of the collagenolytic activity of MMP14. However, as well as collagen I processing, MMP14 can also process several extracellular matrices. We investigated extracellular matrix alterations occurring in the MMP14-deleted fibroblasts that can contribute to the modulation of melanoma growth. The matrix deposited by cultured MMP14-deleted fibroblast displayed an antiproliferative and anti-migratory effect on melanoma cells in vitro. Analysis of the secreted and deposited-decellularized fibroblast's matrix identified a few altered proteins, among which the most significantly changed was collagen XIV. This collagen was increased because of post-translational events, while de novo synthesis was unchanged. Collagen XIV as a substrate was not pro-proliferative, pro-migratory, or adhesive, suggesting a negative regulatory role on melanoma cells. Consistent with that, increasing collagen XIV concentration in wild-type fibroblast-matrix led to reduced melanoma proliferation, migration, and adhesion. In support of its anti-tumor activity, enhanced accumulation of collagen XIV was detected in peritumoral areas of melanoma grown in mice with the fibroblast's deletion of MMP14. In advanced human melanoma samples, we detected reduced expression of collagen XIV compared to benign nevi, which showed a robust expression of this molecule around melanocytic nests. This study shows that loss of fibroblast-MMP14 affects melanoma growth through altering the peritumoral extracellular matrix (ECM) composition, with collagen XIV being a modulator of melanoma progression and a new proteolytic substrate to MMP14.

Dataset Information

PTMA, a new identified autoantigen for oral submucous fibrosis, regulates oral submucous fibroblast proliferation and extracellular matrix.

Publications

PTMA, a new identified autoantigen for oral submucous fibrosis, regulates oral submucous fibroblast proliferation and extracellular matrix.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets