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Junctional adhesion molecule-A is abnormally expressed in diffuse cutaneous systemic sclerosis skin and mediates myeloid cell adhesion
  1. Yong Hou (houyongjia{at}gmail.com)
  1. Department of Internal Medicine,University of Michigan Medical School, United States
    1. Bradley J Rabquer (brabquer{at}med.umich.edu)
    1. University of Michigan Medical School, United States
      1. Michele L Gerber
      1. University of Michigan Medical School, United States
        1. Francesco Del Galdo
        1. Thomas Jefferson University, United States
          1. Sergio A Jimenez
          1. Thomas Jefferson University, United States
            1. G Kenneth Haines III
            1. Yale University, Department of Pathology, United States
              1. Walter G Barr
              1. Northwestern University Feinberg School of Medicine, United States
                1. Mary C Massa
                1. Rush University Medical Center, Department of Dermatology, United States
                  1. James R Seibold
                  1. Department of Internal Medicine,University of Michigan Medical School, United States
                    1. Alisa E Koch (aekoch{at}umich.edu)
                    1. VA Medical Service, Department of Veterans Affairs, United States

                      Abstract

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

                      Methods: Biopsies from proximal and distal arm skin and serum were obtained from patients with SSc and normal (NL) 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 compared to NL. However, sJAM-A was elevated in the serum of patients with SSc compared to NL. Conversely, JAM-A was increased on the surface of SSc compared to NL 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. While increased JAM-A expression on SSc fibroblasts may serve to retain myeloid cells, which in turn secrete angiogenic factors.

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