Kidney Injury Causes Accumulation of Renal Sodium That Modulates Renal Lymphatic Dynamics.
Kidney Injury Causes Accumulation of Renal Sodium That Modulates Renal Lymphatic Dynamics.
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DOI：
10.3390/ijms23031428
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发表时间：
2022-01-27
影响因子：
5.6
通讯作者：
Kon V
中科院分区：
文献类型：
--
作者：
Liu J;Shelton EL;Crescenzi R;Colvin DC;Kirabo A;Zhong J;Delpire EJ;Yang HC;Kon V
淋巴管对间质环境的变化有高度反应。以前，我们发现肾动脉表达Na-K-2Cl协同转运蛋白。由于间质钠潴留是蛋白尿损伤的标志，我们研究了肾钠是否影响NKCC 1表达和肾淋巴管的动态泵功能。嘌呤霉素氨基糖苷（PAN）注射大鼠作为蛋白尿肾损伤的模型。用~（23）Na/1H-MRI测量活体动物肾脏钠和水含量。收集反映间质组成的肾淋巴液，并分析钠。在灌流室中研究了离体肾淋巴管的收缩动力学。使用培养的淋巴管内皮细胞（LEC）评估钠对NKCC 1的直接影响。MRI显示PAN患者肾钠和水升高。此外，肾淋巴液中含有较高的钠，虽然血浆钠显示PAN和对照组之间没有差异。高钠使肾集合淋巴管收缩力下降。在LEC中，高钠减少磷酸化NKCC 1和SPAK，NKCC 1的上游活化激酶，以及eNOS，淋巴收缩的下游效应子。与对照组相比，NKCC 1抑制剂速尿对PAN离体肾淋巴管射血分数的影响较弱。蛋白尿损伤后肾髓质内的高钠与肾淋巴泵功能受损相关，这可能部分涉及SPAK-NKCC 1-eNOS通路，这可能有助于钠潴留并降低淋巴对呋塞米的反应性。我们认为，这种淋巴管功能障碍是蛋白尿肾病间质清除受损和水肿的一种新机制。
Lymphatic vessels are highly responsive to changes in the interstitial environment. Previously, we showed renal lymphatics express the Na-K-2Cl cotransporter. Since interstitial sodium retention is a hallmark of proteinuric injury, we examined whether renal sodium affects NKCC1 expression and the dynamic pumping function of renal lymphatic vessels. Puromycin aminonucleoside (PAN)-injected rats served as a model of proteinuric kidney injury. Sodium 23Na/1H-MRI was used to measure renal sodium and water content in live animals. Renal lymph, which reflects the interstitial composition, was collected, and the sodium analyzed. The contractile dynamics of isolated renal lymphatic vessels were studied in a perfusion chamber. Cultured lymphatic endothelial cells (LECs) were used to assess direct sodium effects on NKCC1. MRI showed elevation in renal sodium and water in PAN. In addition, renal lymph contained higher sodium, although the plasma sodium showed no difference between PAN and controls. High sodium decreased contractility of renal collecting lymphatic vessels. In LECs, high sodium reduced phosphorylated NKCC1 and SPAK, an upstream activating kinase of NKCC1, and eNOS, a downstream effector of lymphatic contractility. The NKCC1 inhibitor furosemide showed a weaker effect on ejection fraction in isolated renal lymphatics of PAN vs controls. High sodium within the renal interstitium following proteinuric injury is associated with impaired renal lymphatic pumping that may, in part, involve the SPAK-NKCC1-eNOS pathway, which may contribute to sodium retention and reduce lymphatic responsiveness to furosemide. We propose that this lymphatic vessel dysfunction is a novel mechanism of impaired interstitial clearance and edema in proteinuric kidney disease.
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影响因子：
81.5
作者：
Matthay, Michael A.;Zemans, Rachel L.;Calfee, Carolyn S.
通讯作者：
Calfee, Carolyn S.
扩大的肾脏淋巴管改善了肾脏损伤后的恢复。
影响因子：
2.5
作者：
Baranwal G;Creed HA;Black LM;Auger A;Quach AM;Vegiraju R;Eckenrode HE;Agarwal A;Rutkowski JM
通讯作者：
Rutkowski JM
影响因子：
5.5
作者：
Li Y;Wu X;Mao Y;Liu C;Wu Y;Tang J;Zhao K;Li P
通讯作者：
Li P
影响因子：
82.9
作者：
Kerjaschki, D;Huttary, N;Mazal, PR
通讯作者：
Mazal, PR
影响因子：
16.6
作者：
Rossitto, Giacomo;Mary, Sheon;Delles, Christian
通讯作者：
Delles, Christian