Endogenous Nerve Growth Factor Regulates Collagen Expression and Bladder Hypertrophy through Akt and MAPK Pathways during Cystitis

被引:35
作者
Chung, Chul-Won [1 ]
Zhang, Qing L. [1 ]
Qiao, Li-Ya [1 ]
机构
[1] Virginia Commonwealth Univ, Sch Med, Dept Physiol & Biophys, Richmond, VA 23298 USA
基金
美国国家卫生研究院;
关键词
GENE-RELATED PEPTIDE; NEUROTROPHIC FACTOR; URINARY-BLADDER; HEMORRHAGIC CYSTITIS; SIGNAL-TRANSDUCTION; PROTEIN-KINASE; UP-REGULATION; SUBSTANCE-P; C-JUN; ACTIVATION;
D O I
10.1074/jbc.M109.040444
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Type I collagen forms the main constituent of the extracellular matrix in visceral organs. We reported here that cyclophosphamide (CYP)-induced cystitis significantly increased the production of type I collagen in the inflamed bladder leading to increases in the bladder weight and the thickness of the bladder wall. The endogenous nerve growth factor (NGF) in the urinary bladder regulated type I collagen expression because the neutralizing NGF antibody attenuated cystitis-induced type I collagen up-regulation in the inflamed bladder. Neutralizing NGF antibody also subsequently reversed cystitis-induced increases in bladder weight. Further studies on the intermediate signaling pathways mediating NGF-induced type I collagen expression in the inflamed bladder during cystitis revealed that Akt, JNK, and ERK1/2 activities were increased in the inflamed bladder, whereas p38 MAPK remained unchanged. Suppression of endogenous NGF level with neutralizing NGF antibody significantly blocked the increased activity of Akt, JNK, and ERK1/2 in the inflamed bladder during cystitis. These results indicate that endogenous NGF plays an important role in the activation of Akt and MAPK in the urinary bladder and in bladder hypertrophy during cystitis.
引用
收藏
页码:4206 / 4212
页数:7
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