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Neuropilin 2 Is a Novel Regulator of Distal Colon Contractility

  • George Lambrinos
    Affiliations
    Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts
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  • Vivian Cristofaro
    Affiliations
    Department of Surgery, Harvard Medical School, Boston, Massachusetts

    Division of Urology, VA Boston Healthcare System, Boston, Massachusetts
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  • Kristine Pelton
    Affiliations
    Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts
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  • Alexander Bigger-Allen
    Affiliations
    Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts

    Biological and Biomedical Sciences Program, Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts
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  • Claire Doyle
    Affiliations
    Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts
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  • Evalynn Vasquez
    Affiliations
    Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts
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  • Diane R. Bielenberg
    Affiliations
    Department of Surgery, Harvard Medical School, Boston, Massachusetts

    Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts
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  • Maryrose P. Sullivan
    Correspondence
    Address correspondence to Maryrose P. Sullivan, Ph.D., Urology Research, Bldg. 3, 2C108, Veterans Affairs Boston Healthcare System, 1400 VFW Parkway, West Roxbury, MA 02132; or Rosalyn M. Adam, Ph.D., Urological Diseases Research Center, Boston Children's Hospital, Enders Bldg. 1061.4, 300 Longwood Ave., Boston, MA 02115.
    Affiliations
    Department of Surgery, Harvard Medical School, Boston, Massachusetts

    Division of Urology, VA Boston Healthcare System, Boston, Massachusetts
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  • Rosalyn M. Adam
    Correspondence
    Address correspondence to Maryrose P. Sullivan, Ph.D., Urology Research, Bldg. 3, 2C108, Veterans Affairs Boston Healthcare System, 1400 VFW Parkway, West Roxbury, MA 02132; or Rosalyn M. Adam, Ph.D., Urological Diseases Research Center, Boston Children's Hospital, Enders Bldg. 1061.4, 300 Longwood Ave., Boston, MA 02115.
    Affiliations
    Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts

    Department of Surgery, Harvard Medical School, Boston, Massachusetts
    Search for articles by this author
      Appropriate coordination of smooth muscle contraction and relaxation is essential for normal colonic motility. The impact of perturbed motility ranges from moderate in conditions, such as colitis, to potentially fatal in the case of pseudo-obstruction. The mechanisms underlying aberrant motility and the extent to which they can be targeted pharmacologically are incompletely understood. We identified colonic smooth muscle as a major site of expression of neuropilin 2 (Nrp2) in mice and humans. In mice with inducible smooth muscle–specific knockout of Nrp2, we observed an increase in evoked contraction of colonic rings in response to carbachol at 1 and 4 weeks following initiation of deletion. KCl-induced contraction was also increased at 4 weeks. Colonic motility was similarly enhanced, as evidenced by faster bead expulsion in Nrp2-deleted mice versus Nrp2-intact controls. In length-tension analysis of the distal colon, passive tension was similar in Nrp2-deficient and Nrp2-intact mice, but at low strains, active stiffness was greater in Nrp2-deficient animals. Consistent with our findings in conditional Nrp2 mice, Nrp2-null mice also showed increased contractility in response to carbachol and KCl. Evaluation of selected proteins implicated in smooth muscle contraction revealed no significant differences in the level of α-smooth muscle actin, myosin light chain, calponin, or RhoA. Together, these findings identify Nrp2 as a novel regulator of colonic contractility that may be targetable in conditions characterized by dysmotility.
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