Origin of interstitial fibroblasts in an accelerated model of angiotensin II-induced renal fibrosis
Origin of interstitial fibroblasts in an accelerated model of angiotensin II-induced renal fibrosis
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DOI：
10.1016/s0002-9440(10)61208-4
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发表时间：
2005-11-01
影响因子：
6
通讯作者：
Barnes, JL
中科院分区：
文献类型：
--
作者：
Faulkner, JL;Szcykalski, LM;Barnes, JL
为了确定先前的肾损伤是否加速肾小球硬化和间质纤维化的进展，我们检查了哈布毒液损伤后用血管紧张素H治疗大鼠的效果。发病后，我们通过定位α-平滑肌肌动蛋白（α-SMA）阳性和Na+，K+-ATP酶阳性细胞相对于间质空间、肾小管上皮细胞、肾小管基底膜（TBM）和血管结构的位置来检查间质肌成纤维细胞的起源。还通过检查TBM完整性和在活体追踪实验中使用德克萨斯红（TR）-葡聚糖来评估肾小管上皮-间充质转化。α-SMA阳性肌成纤维细胞的染色显着增加，在管周间隙后48小时哈布毒液加血管紧张素II，特别是在血管周围和肾小球周围区域，而肾小管上皮细胞α-SMA阴性。Na+、K+-ATP酶阳性和TR-葡聚糖标记的细胞仅限于肾小管上皮，并被排除在肾小管之外。到第7天和第14天，扩张的间质空间仅含有α-STMA阳性肌成纤维细胞，而没有TR-葡聚糖内吞颗粒。含有TR-葡聚糖的萎缩小管的上皮仍然被周围的结缔组织和肌成纤维细胞限制。这些研究表明，肾小管中a-SMA阳性细胞的早期扩增和肾小管面积的损失通过间质肌成纤维细胞从血管周围侵入萎缩的肾小管空间而发生，而不是通过上皮-间充质转化和肾小管细胞通过TBM迁移到肾小管中。
To determine whether previous renal injury accelerates the progression of glomerulosclerosis and interstitial fibrosis, we examined the effect of treating rats with angiotensin H after Habu venom injury. After initiating disease, we examined the origin of interstitial myofibroblasts by locating a-smooth muscle actin (alpha-SMA)-positive and Na+,K+-ATPase-positive cells relative to interstitial space, tubular epithelial cells, the tubular basement membrane (TBM), and vascular structures. Tubular epithelial-mesenchymal transition was also assessed by examining TBM integrity and by using Texas Red (TR)-dextran in intravital tracking experiments. The staining of alpha-SMA-positive myofibroblasts dramatically increased in peritubular interstitial spaces 48 hours after Habu venom plus angiotensin II, particularly in and around perivascular and periglomerular regions, while tubular epithelial cells were alpha-SMA-negative. Na+,K+-ATPase-positive and TR-dextran-labeled cells were restricted to the tubular epithelium and excluded from the interstitium. By 7 and 14 days, expanded interstitial space contained only alpha-STMA-positive myofibroblasts without TR-dextran endocytic particles. Epithelium of atrophic tubules containing TR-dextran remained confined by surrounding interstitium and myofibroblasts. These studies indicate that early expansion of a-SMA-positive cells in the interstitium and loss of tubular area occur via encroachment of interstitial myofibroblasts from perivascular into atrophic tubular spaces rather than via epithelial-mesenchymal transition and migration of tubular cells through the TBM into the interstitium.