Basic fibroblast growth factor modulates proliferation and collagen expression in urinary bladder smooth muscle cells

Abstract

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.

Basic fibroblast growth factor causes urinary bladder overactivity through gap junction generation in the smooth muscle

“…BSMC were isolated from 9-wk-old female SpragueDawley rats (Japan Slc, Shizuoka, Japan) using a procedure described previously (14,19). Cells after two passages were seeded at 2 ϫ 10 4 cells/ml in six-well plates for Western blot analysis or on chamber slides for immunofluorescence, and then serum-deprived in DMEM containing 0.5% FCS for 48 h before each assay.…”

“…One is the mechanism of connexin 43 upregulation and the other is the functional involvement of connexin 43 in detrusor hypersensitivity. Regarding the former issue, our previous study demonstrated a regulatory effect of basic fibroblast growth factor (bFGF) on BSMC remodeling in the obstructed bladder with specific alterations of collagen production and BSMC proliferation (14). Since bFGF has been reported to stimulate connexin 43 expression in cardiac myocytes and fibroblasts (7,8), we postulated that the same mechanism that regulates collagen production and cell proliferation could also regulate connexin 43 expression in the obstructed bladder.…”

“…Next, the regulatory role of bFGF on connexin 43 expression in BSMC was investigated using an in vitro BSMC culture system. Finally, the physiological effects of bFGF on bladder smooth muscle were explored in our original in vivo animal model, where a gelatin hydrogel incorporating bFGF was employed as a carrier for sustained release (14,15,32,35,36).…”

Full-Thickness Hysterocystoplasty for Management of a Large Bladder Defect: Experimental Study in Goats

“…At the same time, the elasticity of the nonshrunken graft should be preserved; this is directly related to development of well-developed and organized smooth muscle bundles derived from the edges of the bladder that traverse the graft, organize and then develop into mature muscles [18].…”

Aspects of Urological Tissue Engineering

“…The opposite face of the scaffold could them be modified using a second component, which in this case was a mixture of PGA and urothelial cells, since these cells could potentially send necessary signals to smooth muscle cells during regeneration. (Beqaj, 2005;Imamura, 2007) When the human bladder smooth muscle cells and urothelial cells where embedded in a PA-scaffold with a growth factor (bFGF) and incubated in vivo in a subcutaneous nude rat model, it was found that the human bladder smooth muscle cells were retained and composed the majority of the scaffold cellular content. It was also found that the system which uses a combination of PGA, PA, growth factors and cells demonstrated higher levels of phenotypic alpha-smooth muscle actin than control scaffolds made of PGA and cells only.…”