NOVEL CLASSIFICATION OF RENAL TUBULAR ACIDOSIS BY EXPRESSION OF ACID-BASE RELATED PROTEINS

通过酸碱相关蛋白的表达对肾小管性酸中毒进行新的分类

• 批准号: 08670927
• 负责人: MATSUMOTO Tohru
• 金额: $ 1.47万
• 依托单位: KURUME UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670927/
• 关键词: Nephrogenesis; collecting duct; differentiation; cell polarity; Band III; H-ATPase; intercalated cell; Renal tubular acidosis; RTAI型; RTAII型; BandIII蛋白(HCO3; Cl); 尿中脱落上皮細胞; 腎生検組織

We have performed the basic research to try to make the novel classification of renal tubular acidosis by analyzing the acid-base related proteins. Initially, we have investigated the expression of acid-base related proteins in the kidney with nephrogenesis. Anti-H-ATPase antibody (Ell), anti-Band III antibody (IVF12), PNA are used for the detection of alphatype intercalated cells and beta type intercalated cells. In the newborn rabbit, nephrogenesis still occurred and cell polality with H-ATPase and Band III were not established. Interestingly, with double labeling of Ell and PNA,both Ell and PNA,only Ell, only PNA labeling cell are (94%, 5%, 1%) in 1 week, (82%, 14%, 4%) in 3weeks, and (82%, 12%, 4%) in adult respectively. It was found that in the newborn premature cells were not well differentiated into alpha and beta type intercalated cells. On carbonic anhydrase (CA) staining, all the differentiating mesenchymal cells contain CA but fade it out with renal maturation. CA supposed to become to localize at proximal cells or intercalated cells with age. On the other hand, clinically several patients with RTA I showed less intense staining of H-ATPase Comparing to normal control. Similarly, some of patients with RTA II showed less intense staining of H-ATpase. In IVF12 staining, the patients studied in this study did not show any lack of immunocytochemical staining which suspect Band III deficiency. Because of the immaturity of cell differentiation and unestblishment of cell polality, newborn infant tended to be acid-base disturbance. Furthermore, with regard to acid-base related proteins, lower production of H-ATPase and Band III may in part relate to RTA.In the future, increment of H-ATPase, Band III,or mRNA of acid-related proteins by acid loading will be required for the better understanding of RTA.

本研究进行了基础性研究，试图通过分析酸碱相关蛋白，对肾小管性酸中毒进行新的分类。首先，我们研究了肾发生过程中肾脏酸碱相关蛋白的表达。用抗H-ATP酶抗体（Ell）、抗带III抗体（IVF 12）、PNA检测β型和β型嵌入细胞。在新生兔中，仍发生肾发生，且未建立具有H-ATP酶和带III的细胞极性。有趣的是，E11和PNA双标记、E11和PNA双标记、E11单标记、PNA单标记细胞在1周内分别为94%、5%、1%，在3周内分别为82%、14%、4%，在成体中分别为82%、12%、4%。结果发现，在新生儿中，未成熟细胞不能很好地分化为α和β型闰间细胞。在碳酸酐酶（CA）染色上，所有分化中的间充质细胞都含有CA，但随着肾成熟而逐渐消失。随着年龄的增长，CA可能定位于近端细胞或闰层细胞。而临床上部分RTA Ⅰ患者H-ATP酶染色较正常人弱。同样，一些RTA II患者的H-ATP酶染色强度较低。在IVF 12染色中，本研究中研究的患者未显示任何怀疑带III缺乏的免疫细胞化学染色缺乏。新生儿由于细胞分化不成熟，细胞极性未建立，易发生酸碱失衡。此外，在酸-碱相关蛋白方面，H-ATP酶和Band Ⅲ的低水平表达可能与RTA有关，今后需要通过酸负荷增加H-ATP酶、Band Ⅲ或酸相关蛋白的mRNA来更好地理解RTA。