Promotion of Renal Tubular Regeneration by Follistatin

卵泡抑素促进肾小管再生

• 批准号: 13557083
• 负责人: KOJIMA Itaru
• 金额: $ 9.15万
• 依托单位: Institute for Molecular and Cellular Regulation, Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557083/
• 关键词: follistatin; activin; regeneration medicine; renal tubular cell; apoptosis; growth factor; stem cell; epithelial cell; 腎尿細管

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.

在本研究中，我们研究了激活素-卵泡抑素系统在大鼠肾小管细胞缺血-再灌注后再生中的作用。缺血再灌注后，激活素bA亚基的表达明显上调。组织学上，肾小管细胞缺血再灌注后激活素A的免疫反应性升高。相反，激活素拮抗剂卵泡抑素的表达在缺血再灌注后明显降低。这些结果表明激活素A在缺血再灌注后起主导作用。为了检验激活素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。Follistatin可显著改善缺血再灌注引起的组织学紊乱。因此，卵泡抑素显著减少出血、单核细胞浸润和铸型形成。此外，卵泡抑素可显著减少凋亡细胞的数量。此外，卵泡抑素显著增加了肾小管brdu阳性细胞的数量。与这些结果相一致的是，给予卵泡抑素后血清BUN和肌酐水平显著降低。这些结果表明，激活素A在缺血再灌注后的肾功能障碍中起关键作用，给予卵泡抑素可有效减少肾小管损伤和促进肾小管细胞再生。

项目成果

Maeshima, A., Nojima, Y., Kojima, I.: "The role of the activin-follistatin system in the developmental and regeneration processes of the kidney"Cytokine and Growth Factor Reviews. 12. 289-298 (2001)

Maeshima, A.、Nojima, Y.、Kojima, I.：“激活素-卵泡抑素系统在肾脏发育和再生过程中的作用”细胞因子和生长因子评论。

Maeshima, A., Zhang, Y.Q., Nojima, Y., Naruse, T., Kojima, I.: "Involvement of the activin-follistatin system in tubular regeneration after renal ischemia in rats"J.Am.Soc.Nephrol.. 12. 1685-1695 (2001)

Maeshima, A.、Zhang, Y.Q.、Nojima, Y.、Naruse, T.、Kojima, I.：“激活素-卵泡抑素系统参与大鼠肾缺血后肾小管再生”J.Am.Soc.Nephrol..

Maeshima, A., Nojima, Y., Kojima, I.: "Activin A : an autocrine regulator of cell growth and differentiation in renal proximal tubule"Kidney.Int.. 62. 446-454 (2002)

Maeshima, A.、Nojima, Y.、Kojima, I.：“激活素 A：肾近端小管中细胞生长和分化的自分泌调节剂”Kidney.Int.. 62. 446-454 (2002)

Maeshima, A., Maeshima, K., Nojima, Y., Kojima, I.: "Involvement of Pax-2 in the action of activin A on tubular cell regeneration"J.Am.Soc.Nephrol.. 12. 2850-2859 (2002)

Maeshima, A.、Maeshima, K.、Nojima, Y.、Kojima, I.：“Pax-2 参与激活素 A 对肾小管细胞再生的作用”J.Am.Soc.Nephrol.. 12. 2850-

Zhang, Y.Q., Maeshima, H. and Kojima, I.: "Changes in the expression of transcription factors in AR42J cells during differentiation to insulin-secreting cells"Diabetes. 50. S10-S14 (2001)

张，Y.Q.，前岛，H. 和小岛，I.：“AR42J 细胞分化为胰岛素分泌细胞过程中转录因子表达的变化”糖尿病。