Expanded renal lymphatics improve recovery following kidney injury.
Expanded renal lymphatics improve recovery following kidney injury.
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扩大的肾脏淋巴管改善了肾脏损伤后的恢复。
DOI：
10.14814/phy2.15094
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发表时间：
2021-11
影响因子：
2.5
通讯作者：
Rutkowski JM
中科院分区：
文献类型：
--
作者：
Baranwal G;Creed HA;Black LM;Auger A;Quach AM;Vegiraju R;Eckenrode HE;Agarwal A;Rutkowski JM
急性肾损伤（AKI）是患者死亡的主要原因，也是慢性肾脏疾病（CKD）进展的主要风险倍增器。AKI向CKD过渡的机制是复杂的，但可能是由初始损伤后炎症反应的程度和长度介导的。淋巴管通过液体、大分子和免疫调节来帮助维持组织稳态。淋巴生长增加，或淋巴管生成，经常发生在炎症期间，并在急性和慢性疾病过程中发挥作用。肾淋巴管和淋巴管生成在AKI恢复和CKD进展中的作用仍然很大程度上未知。为了确定增加的淋巴密度是否在肾损伤反应中具有保护作用，我们利用转基因小鼠模型，诱导肾特异性淋巴生成蛋白血管内皮生长因子- D过表达，以扩大肾淋巴。用诱导足细胞凋亡和蛋白尿（POD‐ATTAC）或双侧缺血再灌注损伤“KidVD”小鼠肾脏。在两种模型的急性损伤阶段，通过测定血清肌酐和肾小球滤过率，KidVD小鼠表现出与同窝小鼠相似的功能丧失。虽然最初的炎症反应是相似的，但KidVD小鼠表现出肾脏中更多的CD4+和更少的CD8+ T细胞的转变。随着时间的推移，KidVD小鼠的胶原沉积减少，功能恢复改善。在KidVD - POD - ATTAC小鼠中，损伤后28天计数足细胞数量增加。这些数据表明，损伤前淋巴密度的增加改变了损伤恢复反应，并提供了防止CKD进展的保护。肾损伤前肾淋巴密度增高可改变炎症反应。这似乎改善了急性期后的损伤消退，减少了纤维化和AKI到CKD的进展。
Acute kidney injury (AKI) is a major cause of patient mortality and a major risk multiplier for the progression to chronic kidney disease (CKD). The mechanism of the AKI to CKD transition is complex but is likely mediated by the extent and length of the inflammatory response following the initial injury. Lymphatic vessels help to maintain tissue homeostasis through fluid, macromolecule, and immune modulation. Increased lymphatic growth, or lymphangiogenesis, often occurs during inflammation and plays a role in acute and chronic disease processes. What roles renal lymphatics and lymphangiogenesis play in AKI recovery and CKD progression remains largely unknown. To determine if the increased lymphatic density is protective in the response to kidney injury, we utilized a transgenic mouse model with inducible, kidney‐specific overexpression of the lymphangiogenic protein vascular endothelial growth factor‐D to expand renal lymphatics. “KidVD” mouse kidneys were injured using inducible podocyte apoptosis and proteinuria (POD‐ATTAC) or bilateral ischemia reperfusion. In the acute injury phase of both models, KidVD mice demonstrated a similar loss of function measured by serum creatinine and glomerular filtration rate compared to their littermates. While the initial inflammatory response was similar, KidVD mice demonstrated a shift toward more CD4+ and fewer CD8+ T cells in the kidney. Reduced collagen deposition and improved functional recovery over time was also identified in KidVD mice. In KidVD‐POD‐ATTAC mice, an increased number of podocytes were counted at 28 days post‐injury. These data demonstrate that increased lymphatic density prior to injury alters the injury recovery response and affords protection from CKD progression. Increased renal lymphatic density prior to kidney injury alters the inflammatory response. This appears to improve injury resolution beyond the acute phase, reducing fibrosis and the AKI to CKD progression.
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影响因子：
--
作者：
Brown JR;Rezaee ME;Marshall EJ;Matheny ME
通讯作者：
Matheny ME
DOI：
10.1152/ajprenal.00179.2018
发表时间：
2018-10-01
影响因子：
4.2
作者：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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影响因子：
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作者：
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