Basic fibroblast growth factor modulates proliferation and collagen expression in urinary bladder smooth muscle cells
Basic fibroblast growth factor modulates proliferation and collagen expression in urinary bladder smooth muscle cells
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DOI：
10.1152/ajprenal.00107.2007
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发表时间：
2007-10-01
影响因子：
4.2
通讯作者：
Ogawa, Osamu
中科院分区：
文献类型：
--
作者：
Imamura, Masaaki;Kanematsu, Akihiro;Ogawa, Osamu
膀胱肥大是膀胱出口梗阻（BOO）的普遍后果，也是临床泌尿系统疾病（如良性前列腺增生和神经源性膀胱）中观察到的典型现象。其特征是平滑肌增生、细胞外基质组成改变和收缩功能增强。多种生长因子可能参与肥厚的病理生理学，但它们的功能仍然未知。在本报告中，使用大鼠膀胱平滑肌细胞（BSMC）培养系统和原始动物模型研究了碱性成纤维细胞生长因子（bFGF）的作用，其中bFGF从明胶水凝胶中直接释放到大鼠膀胱上。 bFGF 治疗在体外和体内均促进 BSMC 增殖。在体外，bFGF 下调 I 型胶原蛋白的表达，但上调 III 型胶原蛋白的表达。 ERK1/2（而非 p38MAPK）被 bFGF 激活，而 PD98059 对 ERK1/2 的抑制可逆转 bFGF 诱导的 BSMC 增殖、I 型胶原蛋白下调和 III 型胶原蛋白上调。在体内释放模型中，bFGF 上调 III 型胶原并增加治疗膀胱的收缩力。与这些发现平行的是，与假手术大鼠相比，尿道收缩造成的肥大大鼠膀胱显示出尿路上皮 bFGF 表达增加、BSMC 增殖和 III 型胶原表达增加。这些数据表明，来自尿路上皮的 bFGF 可以充当旁分泌信号，刺激 BSMC 的增殖和基质产生，从而有助于平滑肌层的肥大重塑。
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.