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Am J Physiol Renal Physiol 293: F1007-F1017, 2007. First published July 18, 2007; doi:10.1152/ajprenal.00107.2007
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Basic fibroblast growth factor modulates proliferation and collagen expression in urinary bladder smooth muscle cells

Masaaki Imamura,1,2 Akihiro Kanematsu,1 Shingo Yamamoto,3 Yu Kimura,2 Isao Kanatani,1,2 Noriyuki Ito,1 Yasuhiko Tabata,2 and Osamu Ogawa1

1Department of Urology, Graduate School of Medicine, and 2Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto; and 3Department of Urology, Hyogo Medical College, Nishinomiya, Japan

Submitted 1 March 2007 ; accepted in final form 11 July 2007

Bladder hypertrophy is a general consequence of bladder outlet obstruction (BOO) and a typical phenomenon observed in clinical urologic diseases such as benign prostatic hyperplasia and neurogenic bladder. It is characterized by smooth muscle hyperplasia, altered extracellular matrix composition, and increased contractile function. Various growth factors are likely involved in hypertrophic pathophysiology, but their functions remain unknown. In this report, the role of basic fibroblast growth factor (bFGF) was investigated using a rat bladder smooth muscle cell (BSMC) culture system and an original animal model, in which bFGF was released from a gelatin hydrogel directly onto rat bladders. bFGF treatment promoted BSMC proliferation both in vitro and in vivo. In vitro, bFGF downregulated the expression of type I collagen, but upregulated type III collagen. ERK1/2, but not p38MAPK, was activated by bFGF, whereas inhibition of ERK1/2 by PD98059 reversed bFGF-induced BSMC proliferation, type I collagen downregulation, and type III collagen upregulation. In the in vivo release model, bFGF upregulated type III collagen and increased the contractile force of treated bladders. In parallel with these findings, hypertrophied rat bladders created by urethral constriction showed increased urothelial bFGF expression, BSMC proliferation, and increased type III collagen expression compared with sham-operated rats. These data suggest that bFGF from the urothelium could act as a paracrine signal that stimulates the proliferation and matrix production of BSMC, thereby contributing to the hypertrophic remodeling of the smooth muscle layer.

bFGF; bladder smooth muscle cell; type I collagen; type III collagen; ERK



Address for reprint requests and other correspondence: O. Ogawa, Kyoto Univ. Graduate School of Medicine, Shogoin-kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan (e-mail: ogawao{at}kuhp.kyoto-u.ac.jp)







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