Renal Fibrosis, Immune Cell Infiltration and Changes of TRPC Channel Expression after Unilateral Ureteral Obstruction in Trpc6-/- Mice

Kong, Weiying; Haschler, Timo N.; Nürnberg, Bernd; Krämer, Stephanie; Gollasch, Maik; Markó, Lajos

doi:10.33594/000000103

Cited by 18 publications

(31 citation statements)

References 77 publications

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“…In our previous study, we have shown that TRPC6 contributes to renal fibrosis and immune cell infiltration in a murine UUO model using Trpc6 −/− mice 9 . Renal IRI is a common cause of CKD.…”

Section: Discussionmentioning

confidence: 97%

“…In our study, Trpc6 −/− mice subjected to acute IRI showed no difference in renal function or tubular damage when compared to WT mice which underwent IRI. The Trpc6 −/− mouse model was established as a homozygous colony, therefore we used C57BL/6 J mice as control 9 . Given this limitation of our experimental approach and to account for possible confounding genomic and non-genomic effects of other TRPC channels caused by global loss of TRPC6 31 , we performed also studies using two different TRPC6 blockers SH045 and BI-749327 in C57BL/6 J WT mice to evaluate the role of TRPC6 in short-term AKI outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in TRPC6 lead to familial forms of focal segmental glomerulosclerosis (FSGS) and to end stage kidney disease 6 , 7 . Of note, TRPC6 dysregulation is also linked to progression of acquired forms of proteinuric kidney disease 8 , 9 . As a result of the TRPC6 activation, intracellular Ca 2+ concentration in the podocyte increases and ultimately causes programmed cell death leading to progressive kidney failure.…”

Section: Introductionmentioning

confidence: 99%

“…As a result of the TRPC6 activation, intracellular Ca 2+ concentration in the podocyte increases and ultimately causes programmed cell death leading to progressive kidney failure. Recent evidence strongly suggests that TRPC6 also contributes to renal fibrosis and immune cell infiltration in the unilateral ureteral obstruction mouse model of progressive renal interstitial fibrosis 9 , 10 .…”

Section: Introductionmentioning

confidence: 99%

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Role of TRPC6 in kidney damage after acute ischemic kidney injury

Zheng

Tsvetkov

Bartolomaeus

et al. 2022

Sci Rep

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Transient receptor potential channel subfamily C, member 6 (TRPC6), a non-selective cation channel that controls influx of Ca2+ and other monovalent cations into cells, is widely expressed in the kidney. TRPC6 gene variations have been linked to chronic kidney disease but its role in acute kidney injury (AKI) is unknown. Here we aimed to investigate the putative role of TRPC6 channels in AKI. We used Trpc6−/− mice and pharmacological blockade (SH045 and BI-749327), to evaluate short-term AKI outcomes. Here, we demonstrate that neither Trpc6 deficiency nor pharmacological inhibition of TRPC6 influences the short-term outcomes of AKI. Serum markers, renal expression of epithelial damage markers, tubular injury, and renal inflammatory response assessed by the histological analysis were similar in wild-type mice compared to Trpc6−/− mice as well as in vehicle-treated versus SH045- or BI-749327-treated mice. In addition, we also found no effect of TRPC6 modulation on renal arterial myogenic tone by using blockers to perfuse isolated kidneys. Therefore, we conclude that TRPC6 does not play a role in the acute phase of AKI. Our results may have clinical implications for safety and health of humans with TRPC6 gene variations, with respect to mutated TRPC6 channels in the response of the kidney to acute ischemic stimuli.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role of TRPC6 in kidney damage after acute ischemic kidney injury

Zheng

Tsvetkov

Bartolomaeus

et al. 2022

Sci Rep

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“…qRT-PCR was performed as described previously [ 26 ]. Total RNA from snap-frozen kidneys or HK-2 cells was isolated using an RNeasy RNA isolation kit (Qiagen, Australia).…”

Section: Methodsmentioning

confidence: 99%

Hippo-YAP/MCP-1 mediated tubular maladaptive repair promote inflammation in renal failed recovery after ischemic AKI

Zheng

Shao

et al. 2021

Cell Death Dis

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Acute kidney injury (AKI) is associated with significant morbidity and its chronic inflammation contributes to subsequent chronic kidney disease (CKD) development. Yes-associated protein (YAP), the major transcriptional coactivator of the Hippo pathway, has been shown associated with chronic inflammation, but its role and mechanism in AKI-CKD transition remain unclear. Here we aimed to investigate the role of YAP in AKI-induced chronic inflammation. Renal ischemia/reperfusion (I/R) was used to induce a mouse model of AKI-CKD transition. We used verteporfin (VP), a pharmacological inhibitor of YAP, to treat post-IRI mice for a period, and evaluated the influence of YAP inhibition on long-term outcomes of AKI. In our results, severe IRI led to maladaptive tubular repair, macrophages infiltration, and progressive fibrosis. Following AKI, the Hippo pathway was found significantly altered with YAP persistent activation. Besides, tubular YAP activation was associated with the maladaptive repair, also correlated with interstitial macrophage infiltration. Monocyte chemoattractant protein 1 (MCP-1) was found notably upregulated with YAP activation. Of note, pharmacological inhibition of YAP in vivo attenuated renal inflammation, including macrophage infiltration and MCP-1 overexpression. Consistently, in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) induced YAP activation and MCP-1 overproduction whereas these could be inhibited by VP. In addition, we modulated YAP activity by RNA interference, which further confirmed YAP activation enhances MCP-1 expression. Together, we concluded tubular YAP activation with maladaptive repair exacerbates renal inflammation probably via promoting MCP-1 production, which contributes to AKI-CKD transition.

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MulHiST: Multiple Histological Staining for Thick Biological Samples via Unsupervised Image-to-Image Translation

Shi,

Zhang,

Wong

et al. 2023

Lecture Notes in Computer Science

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Renal Fibrosis, Immune Cell Infiltration and Changes of TRPC Channel Expression after Unilateral Ureteral Obstruction in Trpc6-/- Mice

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 18 publications

References 77 publications

Role of TRPC6 in kidney damage after acute ischemic kidney injury

Role of TRPC6 in kidney damage after acute ischemic kidney injury

Hippo-YAP/MCP-1 mediated tubular maladaptive repair promote inflammation in renal failed recovery after ischemic AKI

MulHiST: Multiple Histological Staining for Thick Biological Samples via Unsupervised Image-to-Image Translation

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