CXCL12 and MYC control energy metabolism to support adaptive responses after kidney injury

Yakulov, Toma A.; Todkar, Abhijeet P.; Slanchev, Krasimir; Wiegel, Johannes; Bona, Alexandra; Groß, M.; Scholz, Alexander; Hess, Isabell; Wurditsch, Anne; Grahammer, Florian; Huber, Tobias B.; Lecaudey, Virginie; Bork, Tillmann; Hochrein, Jochen; Boerries, Melanie; Leenders, Justine; Tullio, Pascal De; Jouret, François; Kramer-Zucker, Albrecht; Walz, Gerd

doi:10.1038/s41467-018-06094-4

Cited by 42 publications

(40 citation statements)

References 71 publications

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“…One interesting possible avenue to explore MCC generation subsequent to kidney damage may in fact be the zebrafish kidney. In response to some types of damage, nephrons in the embryonic and adult zebrafish kidney can undergo robust epithelial regeneration (56–62). Exploring if the response to kidney damage entails formation of more MCCs might provide a way to better understand the reparative pathways that are stimulated in injury states.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin signaling regulates renal multiciliated cell specification and maturation

Marra

Adeeb

Chambers

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Multiciliated cells (MCCs) are specialized epithelia with apical bundles of motile cilia that direct fluid flow. MCC dysfunction is associated with human diseases of the respiratory, reproductive, and central nervous systems. Further, the appearance of renal MCCs has been cataloged in several kidney conditions, where their function is unknown. Despite their pivotal health importance, many aspects of MCC development remain poorly understood. Here, we utilized a chemical screen to identify molecules that affect MCC ontogeny in the zebrafish embryo kidney, and found prostaglandin signaling is essential both for renal MCC progenitor formation and terminal differentiation. Moreover, we show that prostaglandin activity is required downstream of the transcription factorets variant 5a(etv5a) during MCC fate choice, where modulating prostaglandin E2(PGE2) levels rescued MCC number. The discovery that prostaglandin signaling mediates renal MCC development has broad implications for other tissues, and could provide insight into a multitude of pathological states.

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Section: Discussionmentioning

confidence: 99%

Prostaglandin signaling regulates renal multiciliated cell specification and maturation

Marra

Adeeb

Chambers

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…The mouse model of renal I/R injury was induced according to the protocol described previously ( Hesketh et al, 2014 ; Yakulov et al, 2018 ). Briefly, mice were anesthetized via intraperitoneal injection of sodium pentobarbital (60 mg/kg) and placed on a heating pad to maintain body temperature at 37°C during surgery.…”

Section: Methodsmentioning

confidence: 99%

Gastrin Attenuates Renal Ischemia/Reperfusion Injury by a PI3K/Akt/Bad-Mediated Anti-apoptosis Signaling

et al. 2020

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Ischemic/reperfusion (I/R) injury is the primary cause of acute kidney injury (AKI). Gastrin, a gastrointestinal hormone, is involved in the regulation of kidney function of sodium excretion. However, whether gastrin has an effect on kidney I/R injury is unknown. Here we show that cholecystokinin B receptor (CCKBR), the gastrin receptor, was significantly up-regulated in I/R-injured mouse kidneys. While pre-administration of gastrin ameliorated I/R-induced renal pathological damage, as reflected by the levels of serum creatinine and blood urea nitrogen, hematoxylin and eosin staining and periodic acid-Schiff staining. The protective effect could be ascribed to the reduced apoptosis for gastrin reduced tubular cell apoptosis both in vivo and in vitro. In vitro studies also showed gastrin preserved the viability of hypoxia/ reoxygenation (H/R)-treated human kidney 2 (HK-2) cells and reduced the lactate dehydrogenase release, which were blocked by CI-988, a specific CCKBR antagonist. Mechanistically, the PI3K/Akt/Bad pathway participates in the pathological process, because gastrin treatment increased phosphorylation of PI3K, Akt and Bad. While in the presence of wortmannin (1 μM), a PI3K inhibitor, the gastrin-induced phosphorylation of Akt after H/R treatment was blocked. Additionally, wortmannin and Akt inhibitor VIII blocked the protective effect of gastrin on viability of HK-2 cells subjected to H/R treatment. These studies reveals that gastrin attenuates kidney I/R injury via a PI3K/Akt/Bad-mediated anti-apoptosis signaling. Thus, gastrin can be considered as a promising drug candidate to prevent AKI.

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“…Adult zebrafish were maintained under standard conditions and embryos were staged according to Kimmel et al (1995). The Transgenic lines Tg(− 8.0cldnb:lynEGFP) zf106 ( cldnb:gfp ) and TgBAC (cxcr4b:H2B-RFP) fu13 ( cxcr4b:H2B-RFP ) have been described previously [31, 32].…”

Section: Methodsmentioning

confidence: 99%

Standardized mounting method of (zebrafish) embryos using a 3D-printed stamp for high-content, semi-automated confocal imaging

Kleinhans

Lecaudey

2019

BMC Biotechnol

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BackgroundDevelopmental biology relies to a large extent on the observation and comparison of phenotypic traits through time using high resolution microscopes. In this context, transparent model organisms such as the zebrafish Danio rerio in which developing tissues and organs can be easily observed and imaged using fluorescent proteins have become very popular. One limiting factor however is the acquisition of a sufficient amount of data, in standardized and reproducible conditions, to allow robust quantitative analysis. One way to improve this is by developing mounting methods to increase the number of embryos that can be imaged simultaneously in near-to-identical orientation.ResultsHere we present an improved mounting method allowing semi-automated and high-content imaging of zebrafish embryos. It is based on a 3D-printed stamp which is used to create a 2D coordinate system of multiple μ-wells in an agarose cast. Each μ-well models a negative of the average zebrafish embryo morphology between 22 and 96 h-post-fertilization. Due to this standardized and reproducible arrangement, it is possible to define a custom well plate in the respective imaging software that allows for a semi-automated imaging process. Furthermore, the improvement in Z-orientation significantly reduces post-processing and improves comparability of volumetric data while reducing light exposure and thus photo-bleaching and photo-toxicity, and improving signal-to-noise ratio (SNR).ConclusionsWe present here a new method that allows to standardize and improve mounting and imaging of embryos. The 3D-printed stamp creates a 2D coordinate system of μ-wells in an agarose cast thus standardizing specimen mounting and allowing high-content imaging of up to 44 live or mounted zebrafish embryos simultaneously in a semi-automated, well-plate like manner on inverted confocal microscopes. In summary, image data quality and acquisition efficiency (amount of data per time) are significantly improved. The latter might also be crucial when using the services of a microscopy facility.

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CXCL12 and MYC control energy metabolism to support adaptive responses after kidney injury

Cited by 42 publications

References 71 publications

Prostaglandin signaling regulates renal multiciliated cell specification and maturation

Prostaglandin signaling regulates renal multiciliated cell specification and maturation

Gastrin Attenuates Renal Ischemia/Reperfusion Injury by a PI3K/Akt/Bad-Mediated Anti-apoptosis Signaling

Standardized mounting method of (zebrafish) embryos using a 3D-printed stamp for high-content, semi-automated confocal imaging

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