Twist1 in podocytes ameliorates podocyte injury and proteinuria by limiting CCL2-dependent macrophage infiltration.
Twist1 in podocytes ameliorates podocyte injury and proteinuria by limiting CCL2-dependent macrophage infiltration.
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DOI：
10.1172/jci.insight.148109
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发表时间：
2021-08-09
期刊：
影响因子：
8
通讯作者：
Crowley SD
中科院分区：
文献类型：
--
作者：
Ren J;Xu Y;Lu X;Wang L;Ide S;Hall G;Souma T;Privratsky JR;Spurney RF;Crowley SD
转录因子Twist 1调节可能影响肾脏疾病进展的几个过程，包括上皮细胞分化和炎性细胞因子诱导。足细胞是特化的上皮细胞，表现出免疫细胞的特征，因此可以介导Twist 1对肾小球疾病的独特作用。为了研究Twist 1在蛋白尿肾病期间足细胞中的功能，我们采用了一种条件突变小鼠，其中Twist 1在足细胞中被选择性地消融（Twist 1-PKO）。在肾小球损伤模型中，足细胞Twist 1的缺失增加了蛋白尿、足细胞损伤和足突消失。足细胞中的Twist 1抑制损伤后单核细胞/巨噬细胞的肾积聚和肾小球CCL 2和巨噬细胞因子TNF-α的表达。从足细胞中选择性删除TNF-α对蛋白尿肾病的进展没有影响。相比之下，抑制CCL 2消除了蛋白尿和足细胞损伤的夸大足细胞Twist 1缺失。总的来说，在蛋白尿肾病中，足细胞中的Twist 1通过限制CCL 2诱导来减轻尿白蛋白排泄和足细胞损伤，CCL 2诱导驱动单核细胞/巨噬细胞浸润到损伤的肾小球中。髓样细胞，而不是足细胞，通过分泌TNF-α进一步促进足细胞损伤和肾小球疾病。这些数据突出了足细胞中Twist 1通过减少局部骨髓免疫应答来减轻肾小球损伤的能力。
The transcription factor Twist1 regulates several processes that could impact kidney disease progression, including epithelial cell differentiation and inflammatory cytokine induction. Podocytes are specialized epithelia that exhibit features of immune cells and could therefore mediate unique effects of Twist1 on glomerular disease. To study Twist1 functions in podocytes during proteinuric kidney disease, we employed a conditional mutant mouse in which Twist1 was selectively ablated in podocytes (Twist1-PKO). Deletion of Twist1 in podocytes augmented proteinuria, podocyte injury, and foot process effacement in glomerular injury models. Twist1 in podocytes constrained renal accumulation of monocytes/macrophages and glomerular expression of CCL2 and the macrophage cytokine TNF-α after injury. Deletion of TNF-α selectively from podocytes had no impact on the progression of proteinuric nephropathy. By contrast, the inhibition of CCL2 abrogated the exaggeration in proteinuria and podocyte injury accruing from podocyte Twist1 deletion. Collectively, Twist1 in podocytes mitigated urine albumin excretion and podocyte injury in proteinuric kidney diseases by limiting CCL2 induction that drove monocyte/macrophage infiltration into injured glomeruli. Myeloid cells, rather than podocytes, further promoted podocyte injury and glomerular disease by secreting TNF-α. These data highlight the capacity of Twist1 in the podocyte to mitigate glomerular injury by curtailing the local myeloid immune response.
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影响因子：
12.8
作者：
Chalmers SA;Chitu V;Herlitz LC;Sahu R;Stanley ER;Putterman C
通讯作者：
Putterman C
影响因子：
82.9
作者：
通讯作者：
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DOI：
10.1016/j.bbadis.2013.08.010
发表时间：
2013-12-01
影响因子：
6.2
作者：
Dolores Sanchez-Nino, Maria;Poveda, Jonay;Ortiz, Alberto
通讯作者：
Ortiz, Alberto
影响因子：
6
作者：
Burt, Davina;Salvidio, Gennaro;Gruden, Gabriella
通讯作者：
Gruden, Gabriella
DOI：
10.1038/labinvest.2010.199
发表时间：
2011-03
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
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