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Junctional adhesion molecule-A is abnormally expressed in diffuse cutaneous systemic sclerosis skin and mediates myeloid cell adhesion
  1. Y Hou1,
  2. B J Rabquer1,
  3. M L Gerber1,
  4. F Del Galdo2,
  5. S A Jimenez2,
  6. G K Haines III3,
  7. W G Barr4,
  8. M C Massa5,
  9. J R Seibold1,
  10. A E Koch1,6
  1. 1
    University of Michigan Medical School, Department of Internal Medicine, Ann Arbor, USA
  2. 2
    Thomas Jefferson University, Jefferson Institute of Molecular Medicine, Philadelphia, USA
  3. 3
    Yale University, Department of Pathology, New Haven, USA
  4. 4
    Northwestern University Feinberg School of Medicine, Department of Internal Medicine, Chicago, USA
  5. 5
    Rush University Medical Center, Department of Dermatology, Chicago, USA
  6. 6
    VA Medical Service, Department of Veterans Affairs, Ann Arbor, USA
  1. Correspondence to Dr B J Rabquer, Divison of Rheumatology, University of Michigan, 109 Zina Pitcher Place, 4418 BSRB Box 2200, Ann Arbor, MI 48109-2200, USA; brabquer{at}


Objective: To investigate the role of junctional adhesion molecule-A (JAM-A) in the pathogenesis of systemic sclerosis (SSc).

Methods: Biopsy specimens from proximal and distal arm skin and serum were obtained from patients with SSc and normal volunteers. To determine the expression of JAM-A on SSc dermal fibroblasts and in SSc skin, cell surface ELISAs and immunohistology were performed. An ELISA was designed to determine the amount of soluble JAM-A (sJAM-A) in serum. Myeloid U937 cell–SSc dermal fibroblast and skin adhesion assays were performed to determine the role of JAM-A in myeloid cell adhesion.

Results: The stratum granulosum and dermal endothelial cells (ECs) from distal arm SSc skin exhibited significantly decreased expression of JAM-A in comparison with normal volunteers. However, sJAM-A was increased in the serum of patients with SSc compared with normal volunteers. Conversely, JAM-A was increased on the surface of SSc compared with normal dermal fibroblasts. JAM-A accounted for a significant portion of U937 binding to SSc dermal fibroblasts. In addition, JAM-A contributed to U937 adhesion to both distal and proximal SSc skin.

Conclusions: JAM-A expression is dysregulated in SSc skin. Decreased expression of JAM-A on SSc ECs may result in a reduced response to proangiogenic basic fibroblast growth factor. Increased JAM-A expression on SSc fibroblasts may serve to retain myeloid cells, which in turn secrete angiogenic factors.

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  • YH and BJR contributed equally to this work.

  • Funding This work was supported by NIH grants AI-40987 and AR-48267, the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, the Frederick G L Huetwell and William D Robinson, MD, Professorship in Rheumatology, Scleroderma Research Foundation, NIH General Clinical Research Center grant M01-RR-00042, NIH Center for Translational Science Activities grant UL1-RR-024986 and by funding from the Scleroderma Center of the University of Michigan.

  • Competing interests None.

  • Ethics approval Ethics committee approval from the University of Michigan.

  • Patient consent Patient consent received.

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