Strain history and TGF-β1 induce urinary bladder wall smooth muscle remodeling and elastogenesis.
Strain history and TGF-β1 induce urinary bladder wall smooth muscle remodeling and elastogenesis.
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DOI：
10.1007/s10237-011-0298-y
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发表时间：
2012-01
影响因子：
3.5
通讯作者：
Sacks, Michael S.
中科院分区：
文献类型：
--
作者：
Heise, Rebecca L.;Parekh, Aron;Joyce, Erinn M.;Chancellor, Michael B.;Sacks, Michael S.
在平滑肌组织中触发病理性重塑的机械线索在很大程度上仍然未知，并且被认为是应变诱导的重塑的关键触发因素。因此，了解机械刺激的影响对于阐明疾病状态的潜在机制和开发平滑肌组织再生方法非常重要。例如，膀胱壁（UBW）对脊髓损伤（SCI）的适应包括广泛的肥大以及胶原蛋白和弹性蛋白的增加，所有这些都深刻地改变了其机械反应。此外，促纤维化生长因子TGF-β1在其他平滑肌组织的病理中上调，并可能导致病理性重塑结果。在本研究中，我们利用离体器官培养系统来研究UBW组织在各种基于应变的机械刺激和外源性TGF-β1下的反应，以评估细胞外基质（ECM）合成、机械反应和膀胱平滑肌细胞（BSMC）表型。结果表明，在15%的应变下，0.5 Hz的应变频率三角波形刺激导致纤维弹性蛋白的产生，胶原蛋白的周转，和更顺应性的ECM。此外，这种拉伸方案诱导细胞表型的变化，而TGF-β1的加入改变了这种表型。被动条生物力学测试进一步证实了这种表型转变，其中用TGF-β1处理的膀胱组比所有其他组更顺应。TGF-β1可增加培养膀胱中可溶性胶原的生成。总的来说，0.5 Hz应变诱导的重塑由于弹性生成而导致顺应性增加，与早期SCI膀胱中所见相似。因此，膀胱条的器官培养物可用作实验模型来检查ECM重塑和细胞表型转变，并可能阐明BMSC单独使用机械拉伸或与生长因子组合使用机械拉伸产生纤维状弹性蛋白的能力。
Mechanical cues that trigger pathological remodeling in smooth muscle tissues remain largely unknown and are thought to be pivotal triggers for strain-induced remodeling. Thus, an understanding of the effects mechanical stimulation is important to elucidate underlying mechanisms of disease states and in the development of methods for smooth muscle tissue regeneration. For example, the urinary bladder wall (UBW) adaptation to spinal cord injury (SCI) includes extensive hypertrophy as well as increased collagen and elastin, all of which profoundly alter its mechanical response. In addition, the pro-fibrotic growth factor TGF-β1 is upregulated in pathologies of other smooth muscle tissues and may contribute to pathological remodeling outcomes. In the present study, we utilized an ex vivo organ culture system to investigate the response of UBW tissue under various strain-based mechanical stimuli and exogenous TGF-β1 to assess extracellular matrix (ECM) synthesis, mechanical responses, and bladder smooth muscle cell (BSMC) phenotype. Results indicated that a 0.5-Hz strain frequency triangular waveform stimulation at 15% strain resulted in fibrillar elastin production, collagen turnover, and a more compliant ECM. Further, this stretch regime induced changes in cell phenotype while the addition of TGF-β1 altered this phenotype. This phenotypic shift was further confirmed by passive strip biomechanical testing, whereby the bladder groups treated with TGF-β1 were more compliant than all other groups. TGF-β1 increased soluble collagen production in the cultured bladders. Overall, the 0.5-Hz strain-induced remodeling caused increased compliance due to elastogenesis, similar to that seen in early SCI bladders. Thus, organ culture of bladder strips can be used as an experimental model to examine ECM remodeling and cellular phenotypic shift and potentially elucidate BMSCs ability to produce fibrillar elastin using mechanical stretch either alone or in combination with growth factors.
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