Promotion of Renal Tubular Regeneration by Follistatin

在本研究中，我们研究了激活素-卵泡抑素系统在大鼠缺血再灌注后肾小管细胞再生中的作用。缺血再灌注后，激活素bA亚单位的表达明显上调。组织学上，缺血再灌注后肾小管细胞中激活素A的免疫反应性增加。相反，激活素拮抗剂卵泡抑素的表达在缺血再灌注后明显减少。这些结果表明，激活素A的作用在缺血-再灌注后变得占主导地位。为了研究激活素A在这一过程中的作用，我们在再灌注后立即给予卵泡抑素。卵泡抑素显著改善缺血再灌注引起的组织学紊乱。因此，出血，单核细胞浸润和管型形成显着减少卵泡抑素。此外，凋亡细胞的数量显着减少卵泡抑素。此外，卵泡抑素还能显著增加肾小管BrdU阳性细胞的数量。与上述结果相一致，给予卵泡抑素可显著降低血清BUN和肌酐水平。这些结果表明，激活素A在缺血再灌注后肾功能不全中起关键作用，并且给予卵泡抑素在减轻肾小管损伤和促进肾小管细胞再生方面均有效。

In the present study, we investigated the involvement of the activin-follistatin system in the regeneration of renal tubular cells after ischemia-reperfusion in rats. After ishcemia- reperfusion, the expression of the bA subunit of activin was markedly up-regulated. Histologically, immunoreactivity of activin A was increased in renal tubular cells after ischemia-reperfusion. In contrast, the expression of follistatin, an activin antagonist, was markedky reduced after ischemia-reperfusion. These results suggest that the effect of activin A becomes dominant after ischemia-reperfusion. To examine the role of activin A in this process, we administered follistatin immediately after reperfusion. Follistatin significantly improved histological derangements induced by ischemia-reperfusion. Thus, bleeding, monocytic infiltration and cast formation were markedly reduced by follistatin. Furthermore, the number of apoptotic cells was markedly reduced by follistatin. In addition, follistatin greatly incresed the number of BrdU-positive cells in renal tubule. In accoradance with these results, the serum BUN and creatinine levels were significantly reduced by the adminstartion of follistatin. These results indicate that activin A plays a critical role in the renal dysfunction after ischemia-reperfusion and adminstration of follistatin is effective in both reduction of tubular damages and promotion of tubular cell regeneration.