SMP-534 inhibits TGF-β-induced ECM production in fibroblast cells and reduces mesangial matrix accumulation in experimental glomerulonephritis
SMP-534 inhibits TGF-β-induced ECM production in fibroblast cells and reduces mesangial matrix accumulation in experimental glomerulonephritis
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DOI：
10.1152/ajprenal.00065.2005
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发表时间：
2005-11-01
影响因子：
4.2
通讯作者：
Taiji, M
中科院分区：
文献类型：
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作者：
Sugaru, E;Sakai, M;Taiji, M
转化生长因子-β (TGF-β) 是一种有效的纤维化因子，负责细胞外基质 (ECM) 的合成，并且是慢性纤维化（包括肾脏）发病机制的主要决定因素。新型小化合物 SMP-534 可减少成纤维细胞中 TGF-β 诱导的 ECM 产生。 SMP-534 抑制 TGF-β 诱导的 p38 丝裂原激活蛋白激酶 (p38) 激活，但不抑制表皮生长因子 (EGF) 诱导的细胞外信号相关激酶 (ERK) 激活。我们还发现，在大鼠抗 Thy-1 肾炎模型中，口服 SMP-534 剂量依赖性地降低肾脏皮质区域的羟脯氨酸含量。在肾脏切片的高碘酸希夫染色中，SMP-534 处理减少了 ECM 积累。这些数据表明 SMP-534 具有治疗纤维化疾病（包括肾病）的潜力。
Transforming growth factor-beta (TGF-beta) is a potent fibrotic factor responsible for the synthesis of extracellular matrix (ECM) and is implicated as the major determinant in pathogenesis of chronic fibroses, including kidney. The novel small compound SMP-534 reduced ECM production induced by TGF-beta in fibroblast cells. SMP-534 inhibited TGF-beta-induced p38 mitogenactivated protein kinase (p38) activation but did not inhibit epidermal growth factor (EGF)- induced extracellular signal-related kinase (ERK) activation. We also found that oral administration of SMP- 534 dose dependently lowered hydroxyproline contents in the cortical region of the kidney in rat anti-Thy-1 nephritis models. In periodic acid-Schiff staining of kidney sections, ECM accumulation was reduced by SMP- 534 treatment. These data indicate that SMP- 534 has potential in therapy for fibrotic diseases, including nephropathy.