Renal extracellular matrix accumulation in acute puromycin aminonucleoside nephrosis in rats.
Renal extracellular matrix accumulation in acute puromycin aminonucleoside nephrosis in rats.
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大鼠急性嘌呤霉素氨基核苷肾病肾细胞外基质积聚。
作者：
Colin L. Jones;S. Buch;M. Post;Lori McCulloch;E. Liu;A. Eddy
进行性肾纤维化被认为是导致慢性肾功能不全的最终共同途径。在这项研究中，作者使用嘌呤霉素氨基核苷（PAN）肾病大鼠作为急性模型系统，研究了调节细胞外基质（ECM）蛋白在肾脏蓄积的一些细胞和分子机制。嘌呤霉素氨基糖苷类大鼠发生可逆性肾病综合征，伴有单核细胞间质浸润。表达ST 4抗原的间质成纤维细胞的数量没有增加。在最初的4天内，所有检测基因的稳态mRNA水平保持在或低于对照水平。在1周时，建立肾病综合征和间质性炎症，并发生一段时间的肾细胞增殖，通过组蛋白mRNA水平增加和氚化胸腺嘧啶放射自显影定位于肾小管上皮细胞和偶尔的间质细胞来鉴定。转化生长因子-β（TGF-β）稳态mRNA水平增加了8倍，但在3周时恢复到对照水平。在第1周，编码间质基质蛋白胶原蛋白I和纤连蛋白以及基底膜胶原蛋白IV的基因的肾脏稳态mRNA水平增加了10至20倍。通过原位杂交，α 1（I）前胶原mRNA定位于间质细胞。免疫荧光显微镜检查显示，在2周和3周时，ECM蛋白在肾小管间质隔室中局灶性积聚，但到6周时，肾脏免疫组织学再次正常。基质降解金属蛋白酶基质溶解素的稳态mRNA水平保持在对照值，而间质胶原酶的水平在第1周是正常的，在第2周和第3周增加了2倍至3倍。金属蛋白酶组织抑制剂（TIMP）的稳态mRNA水平在1周时增加了5倍，并在接下来的2周内恢复到基线值。本研究的结果表明，由于编码多种基质蛋白的基因的激活和TIMP介导的基质降解的抑制，急性PAN肾病大鼠中发生了肾小管间质ECM积聚。这些事件在肾病综合征的恢复期逆转。TGF-β的mRNA水平增加，可能来源于炎性间质单核细胞，可能是观察到的分子事件的介质之一。
Progressive renal fibrosis is considered to be the final common pathway leading to chronic renal insufficiency. In this study, the authors examined some of the cellular and molecular mechanisms regulating the renal accumulation of extracellular matrix (ECM) proteins using rats with puromycin amino-nucleoside (PAN) nephrosis as an acute model system. Puromycin aminonucleoside rats developed reversible nephrotic syndrome accompanied by an interstitial infiltrate of monocytes. The number of interstitial fibroblasts expressing ST4 antigen did not increase. During the first 4 days, steady-state mRNA levels for all genes examined remained at or below control levels. At 1 week, nephrotic syndrome and interstitial inflammation were established, and a period of renal cell proliferation occurred, identified by increased histone mRNA levels and localized by tritiated thymine autoradiography to tubular epithelial cells and occasional interstitial cells. Transforming growth factor-beta (TGF-beta) steady-state mRNA levels were increased eightfold, but returned to control levels by 3 weeks. At week 1, there was a 10- to 20-fold increase in kidney steady-state mRNA levels for genes encoding interstitial matrix proteins collagen I and fibronectin and basement membrane collagen IV. By in situ hybridization, alpha 1(I) procollagen mRNA was localized to interstitial cells. Immunofluorescence microscopy demonstrated focal accumulation of ECM proteins in the tubulointerstitial compartment at 2 and 3 weeks, but by 6 weeks, kidney immunohistology was normal again. Steady-state mRNA levels for the matrix degrading metalloproteinase stromelysin remained at control values, whereas the levels for interstitial collagenase were normal at week 1 and increased twofold to threefold at 2 and 3 weeks. Steady-state mRNA levels for the tissue inhibitor of metalloproteinases (TIMP) increased fivefold at 1 week and returned to baseline values over the next 2 weeks. The results of this study suggest that tubulointerstitial ECM accumulation occurs in rats with acute PAN nephrosis because of the activation of genes encoding several matrix proteins and inhibition of matrix degradation mediated by TIMP. These events are reversed during the phase of recovery from nephrotic syndrome. Increased mRNA levels for TGF-beta, possibly originating from inflammatory interstitial monocytes, are likely to be one of the mediators of the molecular events observed.
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DOI：
--
发表时间：
1986-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Ignotz;J. Massagué
通讯作者：
R. Ignotz;J. Massagué
抗体介导的近曲小管细胞增殖。
影响因子：
4.6
作者：
Brodkin,M;Noble,B
通讯作者：
Noble,B
DOI：
10.1172/jci114816
发表时间：
1990-10
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
K. Harris;J. Lefkowith;S. Klahr;G. Schreiner
通讯作者：
K. Harris;J. Lefkowith;S. Klahr;G. Schreiner
生理学和细胞生物学更新：多肽生长因子及其与肾脏疾病的关系。
DOI：
10.1016/s0272-6386(89)80096-4
发表时间：
1989
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Kujubu,DA;Fine,LG
通讯作者：
Fine,LG
急性嘌呤霉素肾病期间必需脂肪酸缺乏可改善晚期肾损伤。
DOI：
10.1152/ajprenal.1989.257.5.f798
发表时间：
1989
期刊：
The American journal of physiology
影响因子：
--
作者：
Diamond,JR;Pesek,I;Ruggieri,S;Karnovsky,MJ
通讯作者：
Karnovsky,MJ