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Nitric Oxide Suppresses Pulmonary Myofibroblast Proliferation and Actin Expression
Author(s) -
Rowland Naomi S,
Rice Nancy A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a510-b
Subject(s) - myofibroblast , microbiology and biotechnology , nitric oxide , fibrosis , cell growth , chemistry , cancer research , biology , pathology , medicine , endocrinology , biochemistry
Myofibroblasts are mesenchymal cells that function in tissue repair. During wound healing myofibroblasts are differentiated in response to cellular signals. Under certain conditions, myofibroblasts persist implicatingthem in various fibroproliferative processes, such as pulmonary interstitial fibrosis. There is limited information regarding the mechanisms that differentiate between pathological and physiological fibroproliferation. Recently, the nitric oxide (NO) signaling pathway has been implicated in the process. Three different isoforms of NOS have been identified: NOS I, NOS II and NOS III. In the current work, we show that pulmonary myofibroblasts specifically express NOS III and inhibition of NOS III activity with Nδ‐nitro‐L‐arginine methyl ester (L‐NAME) has little effect on myofibroblast proliferation. Alternatively, the addition of NO donor S‐nitroso‐N‐acetylpenicillamine (SNAP) decreases cell proliferation. These observed changes in myofibroblast proliferation were also correlated with changes in α smooth muscle actin (ASMA) expression, a hallmark of myofibroblast differentiation. Treatment of cells with SNAP resulted in complete inhibition of ASMA expression. L‐NAME had little effect on basal levels of ASMA expression but eliminated the stimulatory effect of transforming growth factor β. Interestingly, NOS III expression is also decreased in the presence of SNAP suggesting a possible feedback regulatory mechanism for inhibiting cell proliferation. These experiments suggest that NO‐mediated mechanisms are important for mediating phenotypic changes associated with myofibroblast differentiation. Support of the National Institutes of Health and the National Center for Research Resources Grant P20 RR16481 is gratefully acknowledged.