Dataset Information

Adalimumab Induces a Wound Healing Profile in Patients with Hidradenitis Suppurativa by Regulating Macrophage Differentiation and Matrix Metalloproteinase Expression

ABSTRACT: Adalimumab (ADA) is the only FDA-approved treatment for moderate-to-severe hidradenitis suppurativa (HS), whereas etanercept (ETN) and certolizumab-pegol (CZP) have been shown to be ineffective, suggesting that the mechanism of action of ADA is distinct in HS and may contribute to improved wound healing. Given that macrophages (Mφ) play pivotal roles throughout the wound healing process, an in-vitro Mφ differentiation assay was carried out to assess the impact of TNF-anti-TNF complexes on these cells. TNF-ADA complexes exhibited stronger inhibitory effects on inflammatory Mφ differentiation. Moreover, RNA sequencing revealed several unique wound healing profiles for TNF-ADA-treated inflammatory Mφs, which were not observed for those treated with either TNF-ETN or TNF-CZP, including the inhibition of the matrix metallopeptidase (MMP) pathway. In addition, ADA administration was found to significantly reduce the levels of inflammatory MMPs -1 and -9 while promoting wound healing MMP-13 and tissue inhibitor of metalloproteinases 2 (TIMP-2) levels in the circulation of those HS patients who responded to treatment. Our in-vitro findings demonstrate that TNF-ADA-treated inflammatory Mφs exhibit a distinct profile resembling wound healing. Moreover, ADA not only differentially regulates MMP expression in HS patients responding to the therapy but potentially induces a transition to a profile suggestive of wound healing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE166920 | GEO | 2021/04/14

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Proteinases play a pivotal role in wound healing by degrading molecular barriers, regulating cell-matrix interactions and availability of bioactive molecules. Matrix metalloproteinase-13 (MMP-13, collagenase-3) is a wide spectrum proteinase. Its expression and function is linked to the growth and invasion of many epithelial cancers such as squamous cell carcinoma. Moreover, the physiologic expression of MMP-13 is associated e.g. to scarless healing of human fetal skin and adult gingival wounds. While MMP-13 is not found in the normally healing skin wounds in human adults, it is expressed in mouse skin during wound healing. Thus, mouse wound healing models can be utilized for studying the role of MMP-13 in the events of wound healing. As the processes such as the migration and proliferation of keratinocytes, angiogenesis, inflammation and activation of fibroblasts are components of wound repair as well as of cancer, many results received from wound healing studies are also adaptable to cancer research. Classically, the process of wound healing can be devided into three phases which are histologically and functionally separate but temporally overlapping: 1) hemostasis and inflammation, 2) re-epithelialization and granulation tissue formation, and 3) matrix remodeling. Granulation tissue is formed into the wound via fibroplasia, angiogenesis and extracellular matrix (ECM) deposition by fibroblasts. Granulation tissue is rich in inflammatory cells, fibroblasts, myofibroblasts and blood vessels. After epidermal recovery, the granulation tissue is resolved via matrix remodeling and cell apoptosis. A sterile viscose cellulose sponge (VCS) characterized by defined size and structure can be used to experimentally induce formation of subcutaneous granulation tissue. Compared to normal granulation tissue, this model allows easy examination of the granulation tissue in its entirety but leaving out epidermal keratinocytes in the sample preparation. In this study, we studied the role of MMP-13 in the formation of mouse VCS-induced granulation tissue. We performed gene expression profiling of the granulation tissue samples of Mmp13-/- (KO) and wild type (WT) mice harvested at day 7, day 14 and day 21 after VCS implantation. Mmp13-/- (KO) mice were generated as described (Inada et al. 2004, PNAS, 101: 17192-17197) and used in these experiments after backcrossing at least seven generations into C57BL6 mice. The WT mice were generated from the backcrossed heterozygote Mmp13-/- (KO) mice. Granulation tissues were harvested at three time points (7d, 14d, 21d) from Mmp13-/- (KO) and WT mice. One sample of each mouse was analyzed (n=3, 7d; n=4, 14d; n=4, 21d; for each genotype). The samples were processed for RNA extraction and Affymetrix 3'IVT DNA microarray gene expression analysis.

Dataset Information

Adalimumab Induces a Wound Healing Profile in Patients with Hidradenitis Suppurativa by Regulating Macrophage Differentiation and Matrix Metalloproteinase Expression

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure