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abstract

abstract

028

TNF-alpha inhibition can prevent smooth-muslce dysfunction following bilateral cavernous nerve injury by upregulating GFAP expression through activation of ERK1/ERK2 signaling

Matsui, H1; Sopko , NA2; Liu, X2; Bivalacqua, TJ3

1: University of Tokyo, Japan; 2: Johns Hopkins School of Medicine, USA; 3: ohns Hopkins School of Medicine, USA

Objective(s); Previously, we demonstrated that upregulation of inflammatory cytokines resulted in impaired penile smooth-muscle relaxation following bilateral cavernous injury (BCNI). Glial fibrillary acidic protein (GFAP) is shown to induce Schwann-cell mediated nerve regeneration. GFAP is upregulated by activating extracellular signal-regulated kinase (ERK) signaling. The present study examines whether inhibition of tumor necrosis factor alpha (TNFA) signaling can enhance ERK and GFAP expression and, thus, prevent smooth-muscle dysfunction following BCNI.

Material and Method(s); Wild type (WT) and TNFA receptor knock-out (TNFRKO) mice underwent BCNI or sham surgery (n=6/group). We harvested major pelvic ganglia (MPGs) and penes 4 days after surgery. Penes were used to evaluate parasympathetic-nerve mediated relaxation by electrical field stimulation (EFS) after pre-contraction induced by phenylephrine 1.0 x 10-4 M. MPGs were processed to evaluate gene expression of ERK1, ERK2, and GFAP.

Result(s); BCNI impaired relaxation of penises by EFS following pre-contraction by phenylephrine (p<0.05) but it did not affect relaxation response of penises from TNFRKO mice. qPCR showed that gene expression of ERK1 and ERK2 is significantly upregulated in TNFRKO mice. In addition, upregulation of GFAP gene expression was significantly enhanced in TNFRKO mice.

Conclusion(s); BCNI impaired parasympathetic-mediated relaxation response of penile smooth muscle in WT mice. However, this change was not seen in in TNFRKO mice. TNFRKO mice demonstrated enhanced gene expression of ERK1, ERK2 and GFAP. Findings from this study suggest that TNFA inhibition may promote cavernous nerve regeneration by upreglutaion of GFAP through activation of ERK1/ERK2 pathway.

Disclosure:

Work supported by industry: no.

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