Transforming growth factor-β in acute renal failure:: receptor expression, effects on proliferation, cellularity, and vascularization after recovery from injury
Transforming growth factor-β in acute renal failure:: receptor expression, effects on proliferation, cellularity, and vascularization after recovery from injury
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DOI：
10.1152/ajprenal.00330.2004
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发表时间：
2005-03-01
影响因子：
4.2
通讯作者：
Basile, DP
中科院分区：
文献类型：
--
作者：
Spurgeon, KR;Donohoe, DL;Basile, DP
在大鼠缺血性急性肾功能衰竭（ARF）诱导后，转化生长因子(TGF)- β 1和一些TGF- β应答基因会短暂增强。采用核糖核酸酶保护、原位杂交和免疫组化等方法分析了缺血后大鼠肾脏中tgf - β受体mRNA和蛋白的表达。tgf - β I和-RII在缺血再灌注（I/R）损伤后3天内升高，并在I/R后7天内保持升高；tgf - β受体的表达主要局限于外髓质的再生小管。中和性tgf - β抗体在缺血后第3天观察到细胞增殖加剧，但在第1天或第2天没有影响。在术后35天内，tgf - β抗体治疗对肾功能丧失或肾功能恢复没有可测量的影响。然而，缺血性损伤导致轻度肾肥大，部分原因是缺血后肾脏间质细胞数量增加。免疫组织化学显示，其中一些细胞的成纤维细胞特异性标记物S100A4呈阳性。抗tgf - β治疗显著减轻i /R后35天出现的肾肥大、间质细胞和s100a4阳性细胞。最后，tgf - β免疫中和可减轻I/R损伤恢复后肾血管密度的损失。这些数据表明，tgf - β /TbetaR系统在缺血后肾脏中增强。然而，目前的研究未能确定该系统在ARF后近端小管修复中的突出作用。相反，该系统的激活可能通过影响微血管结构和间质细胞在缺血后肾脏的长期结构中发挥重要作用。
Transforming growth factor (TGF)-beta1 and a number of TGF-beta-responsive genes are transiently enhanced following induction of ischemic acute renal failure (ARF) in the rat. The mRNA and protein expression of TGF-beta receptors were analyzed in postischemic rat kidneys by ribonuclease protection, in situ hybridization, and immunohistochemistry. TGF-betaRI and -RII were enhanced within 3 days of ischemia-reperfusion (I/R) injury and remained elevated for up 7 days post-I/R; TGF-beta receptor expression was localized primarily in regenerating tubules within the outer medulla. A neutralizing TGF-beta antibody exacerbated cellular proliferation observed on day 3 postischemia but had no effect on day 1 or 2. TGF-beta antibody treatment had no measurable effect on loss of renal function or the restoration of renal function during the recovery response for up to 35 days postsurgery. However, ischemic injury resulted in modest renal hypertrophy that is due, in part, to in an increase in the number of interstitial cells in the postischemic kidney. Immunohistochemistry showed that several of these cells stained positively for the fibroblast-specific marker, S100A4 positive. Anti-TGF-beta treatment substantially attenuated the renal hypertrophy, interstitial cellularity, and S100A4-positive cells present at 35 days post-I/R. Finally, TGF-beta immuno-neutralization attenuated the loss of renal vascular density following recovery from I/R injury. These data suggest that the TGF-beta/TbetaR system is enhanced in the postischemic kidney. However, the current study failed to identify a prominent role for this system in the repair of proximal tubules following ARF. In contrast, the activation of this system may play an important role in the long-term structure of the postischemic kidney by influencing microvascular structure and interstitial cellularity.