Endogenous nerve growth factor regulates collagen expression and bladder hypertrophy through Akt and MAPK pathways during cystitis.
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.
Chung
Chul-Won
CW
From the Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0551.
Zhang
Qing L
QL
From the Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0551.
Qiao
Li-Ya
LY
From the Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298-0551. Electronic address: lqiao2@vcu.edu.
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006984:Hypertrophy; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000906:Antibodies; D024042:Collagen Type I; D003520:Cyclophosphamide; D020932:Nerve Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases