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转化生长因子-β及潜在转化生长因子-β结合蛋白在大鼠肾脏中的定位

Localization of transforming growth factor-beta and latent transforming growth factor-beta binding protein in rat kidney.

作者信息

Ando T, Okuda S, Tamaki K, Yoshitomi K, Fujishima M

机构信息

Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

出版信息

Kidney Int. 1995 Mar;47(3):733-9. doi: 10.1038/ki.1995.112.

DOI:10.1038/ki.1995.112
PMID:7752571
Abstract

TGF-beta plays an important role in maintaining the renal histological structure, and glomerular and tubular function. TGF-beta is usually secreted in a biologically inactive or latent form with high molecular weight by normal cells. The latent form of TGF-beta is composed of three distinct components: (a) mature TGF-beta (b) TGF-beta latency associated peptide (LAP) (c) latent TGF-beta binding protein (LTBP). LTBP plays a central role in the assembly, secretion and activation of TGF-beta 1. Most cells secrete a large latent TGF-beta with LTBP, while the other cells secrete a small latent TGF-beta without LTBP. However, the precise localization of TGF-beta and LTBP in the kidney is still not known. In the present study, we used the reverse transcription in combination with polymerase chain reaction (RT-PCR) to investigate the precise localization of TGF-beta 1 and LTBP in the microdissected glomeruli, renal tubules and arterioles. Our findings showed that TGF-beta 1 mRNA was detected in all nephron segments, glomeruli, and arterioles. On the other hand, LTBP mRNA was present in the glomeruli and arterioles, while it was absent in every segment of the renal tubules. Moreover, the immunohistochemical study of LTBP showed that the LTBP protein was localized on the glomeruli and arterioles but not on the renal tubules at the same localization as LTBP mRNA. These results indicate that the tubular epithelial cells secrete the small latent TGF-beta 1, while glomerular cells secrete the large latent TGF-beta 1, suggesting that they both have different structures and thus potentially different biological functions.

摘要

转化生长因子-β(TGF-β)在维持肾脏组织学结构以及肾小球和肾小管功能方面发挥着重要作用。TGF-β通常由正常细胞以生物无活性或高分子量的潜伏形式分泌。TGF-β的潜伏形式由三个不同的成分组成:(a)成熟的TGF-β;(b)TGF-β潜伏相关肽(LAP);(c)潜伏TGF-β结合蛋白(LTBP)。LTBP在TGF-β1的组装、分泌和激活中起核心作用。大多数细胞分泌与LTBP结合的大量潜伏TGF-β,而其他细胞分泌不与LTBP结合的少量潜伏TGF-β。然而,TGF-β和LTBP在肾脏中的精确定位仍然未知。在本研究中,我们使用逆转录结合聚合酶链反应(RT-PCR)来研究TGF-β1和LTBP在显微切割的肾小球、肾小管和小动脉中的精确定位。我们的研究结果表明,在所有肾单位节段、肾小球和小动脉中均检测到TGF-β1 mRNA。另一方面,LTBP mRNA存在于肾小球和小动脉中,而在肾小管的各个节段中均不存在。此外,LTBP的免疫组织化学研究表明,LTBP蛋白定位于肾小球和小动脉,而不在与LTBP mRNA相同定位的肾小管上。这些结果表明,肾小管上皮细胞分泌少量潜伏TGF-β1,而肾小球细胞分泌大量潜伏TGF-β1,这表明它们具有不同的结构,因此可能具有不同的生物学功能。

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