کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4067490 1604416 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dupuytren's Fibroblast Contractility by Sphingosine-1-Phosphate Is Mediated Through Non-Muscle Myosin II
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی ارتوپدی، پزشکی ورزشی و توانبخشی
پیش نمایش صفحه اول مقاله
Dupuytren's Fibroblast Contractility by Sphingosine-1-Phosphate Is Mediated Through Non-Muscle Myosin II
چکیده انگلیسی

PurposePrevious studies suggest that Dupuytren's disease is caused by fibroblast and myofibroblast contractility within Dupuytren's nodules; however, the stimulus for cell contractility is unknown. Sphingosine-1-phosphate (S1P) is a serum-derived lysophospholipid mediator that enhances cell contractility by activating the S1P receptor, S1P2. It is hypothesized that S1P stimulates Dupuytren's fibroblast contractility through S1P2 activation of non-muscle myosin II (NMMII). This investigation examined the role of S1P and NMMII activation in Dupuytren's disease progression and suggests potential targets for treatment.MethodsWe enmeshed Dupuytren's fibroblasts into fibroblast-populated collagen lattices (FPCLs) and assayed S1P-stimulated FPCL contraction in the presence of the S1P2 receptor inhibitor JTE-013, the Rho kinase inhibitor Y-27632, the myosin light chain kinase inhibitor ML-7, and the NMMII inhibitor blebbistatin. Tissues from Dupuytren's fascia (n = 10) and normal palmar fascia (n = 10) were immunostained for NMMIIA and NMMIIB.ResultsSphingosine-1-phosphate stimulated FPCL contraction in a dose-dependent manner. Inhibition of S1P2 and NMMII prevented S1P-stimulated FPCL contraction. Rho kinase and myosin light chain kinase inhibited both S1P and control FPCL contraction. Dupuytren's nodule fibroblasts robustly expressed NMMIIA and NMMIIB, compared with quiescent-appearing cords and normal palmar fascia.ConclusionsSphingosine-1-phosphate promotes Dupuytren's fibroblast contractility through S1P2, which stimulates activation of NMMII. NMMII isoforms are ubiquitously expressed throughout Dupuytren's nodules, which suggests that nodule fibroblasts are primed to respond to S1P stimulation to cause contracture formation. S1P-promoted activation of NMMII may be a target for disease treatment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Hand Surgery - Volume 35, Issue 10, October 2010, Pages 1580–1588
نویسندگان
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