Endotrophin: A Novel Adipokine Linking Adipose Tissue and Skin Fibrosis in Systemic Sclerosis

Roberta Goncalves Marangoni¹, Jun Wei², Monique E. Hinchcliff¹, Philipp E. Scherer³ and John Varga², ¹Division of Rheumatology, Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, IL, ²Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, IL, ³University of Texas Southwestern Medical Center, Dallas, TX

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Adipokines, fibrosis and systemic sclerosis

Session Information

Date: Tuesday, November 10, 2015

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics Poster II

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Adipocytes and their progenitor cells are embedded in a network of extracellular matrix that plays a role in regulating its function. Type 6 collagen (COL6) is the most highly expressed collagen in differentiated adipocytes and its expression is upregulated in the skin in systemic sclerosis (SSc). The cleavage product of COL6α3, endotrophin, is secreted by mature adipocytes. The recently described adipokine, endotrophin,exerts a major influence locally in adipose tissue and has potential effects on triggering fibrosis and inflammation in both metabolic dysfunction and in growing solid tumors. In SSc, recent findings point to an unrecognized connection between adipose tissue, adipokines, and fibrosis. We, therefore, hypothesize that in SSc abnormal endotrophin expression contributes to dermal fibrosis.

Methods: To examine COL6 expression in SSc skin, we first queried a publicly available data set comprising genome-wide expression data from SSc and healthy control skin biopsy samples. COL6 mRNA expression was also examined in explanted fibroblasts from SSc skin biopsies and healthy controls. Tissue levels of endotrophin protein in skin biopsy samples from SSc patients with diffuse subtype and healthy controls were examined by immunohistochemistry.

Results: Levels of COL6 mRNA were found to be significantly increased (p < 0.001) in skin biopsy samples mapping to the diffuse-proliferative and inflammatory intrinsic subsets compared to normal-like subsets. Expression levels of COL6α3 mRNA were positively correlated with the total skin score (MRSS) (R=0.39, p<0.001). Elevated COL6 mRNA expression in SSc skin biopsy samples was confirmed by real-time qPCR (p=0.02). Endotrophin was markedly increased in both dermis and intradermal adipose tissue of diffuse SSc patients as compared to healthy controls (p=0.002).

Conclusion: Endotrophin and COL6 expression are both highly expressed in the skin in SSc. Endotrophin has potential effects on fibrosis in SSc and might be a potential target of therapy.

Disclosure: R. G. Marangoni, None; J. Wei, None; M. E. Hinchcliff, None; P. E. Scherer, None; J. Varga, None.

To cite this abstract in AMA style:

Marangoni RG, Wei J, Hinchcliff ME, Scherer PE, Varga J. Endotrophin: A Novel Adipokine Linking Adipose Tissue and Skin Fibrosis in Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/endotrophin-a-novel-adipokine-linking-adipose-tissue-and-skin-fibrosis-in-systemic-sclerosis/. Accessed .

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