Inducible glomerular erythropoietin production in the adult kidney

Gerl, Katharina; Miquerol, Lucile; Todorov, Vladimir; Hugo, Christian; Adams, Ralf H.; Kurtz, Armin; Kurt, Birgül

doi:10.1038/ki.2015.274

Cited by 63 publications

(54 citation statements)

References 74 publications

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“…To study calcium dynamics in mural cells, we crossed Pdgfrβ-CreERT2 mice (Gerl et al, 2015)) with stop-flox GCaMP6s reporter mice ( Figure 1A). For localization and classification of mural cells, we defined the vessel types based on their branch order and diameter.…”

Section: Two-photon Imaging Of Pdgfrβ-driven Gcamp6s In Mural Cellsmentioning

confidence: 99%

“…license ZH 169/17) and conformed to the guidelines of the Swiss Animal Protection Law, Swiss Veterinary Office, Canton of Zürich (Animal Welfare Act of 16 December 2005 and Animal Protection Ordinance of 23 April 2008). The following mice were interbred: B6.Cg-Tg(Pdgfrb-CreERT2)6096Rha/J (Pdgfrb-CreERT2), The Jackson Laboratory (Stock #029684,Gerl et al, 2015) with Ai96 (GCaMP6s), The Jackson Laboratory (Stock #028866).…”

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confidence: 99%

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Distinct signatures of calcium activity in brain pericytes

Glück

Ferrari

Keller

et al. 2020

Preprint

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Even though pericytes have been implicated in various neurological disorders, little is known about their function and signaling pathways in the healthy brain. Here, we characterized cortical pericyte calcium dynamics using two-photon imaging of Pdgfrβ-CreERT2;GCaMP6s mice under anesthesia in vivo and in brain slices ex vivo. We found distinct differences between pericyte subtypes in vivo: Ensheathing pericytes exhibited smooth muscle cell-like calcium dynamics, while calcium signals in capillary pericytes were irregular, higher in frequency and occurred in cellular microdomains. In contrast to ensheathing pericytes, capillary pericytes retained their spontaneous calcium signals during prolonged anesthesia and in the absence of blood flow ex vivo. Chemogenetic activation of neurons in vivo and acute increase of extracellular potassium in brain slices strongly decreased calcium activity in capillary pericytes. We propose that neuronal activity-induced elevations in extracellular potassium suppress calcium activity in capillary pericytes, likely mediated by Kir2.2 and KATP channel activation.

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Section: Two-photon Imaging Of Pdgfrβ-driven Gcamp6s In Mural Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

Distinct signatures of calcium activity in brain pericytes

Glück

Ferrari

Keller

et al. 2020

Preprint

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“…13 It has already been shown that after doxycycline induction, the expression of reporter genes is correctly targeted to the JG cells of kidneys of adult mRen-rtTA2/ LC1 mice with almost 80% efficiency. 11,14 Here, we used the firefly luciferase activity as a surrogate marker to screen the inducibility of the mRen-rtTAm2 construct throughout different Figure 1. Induction of Gsa deficiency in JG cells of kidneys of adult mice.…”

Section: Induction Of Gsa Deficiency In Kidney Jg Cells Of Adult Micementioning

confidence: 99%

Interference with Gsα-Coupled Receptor Signaling in Renin-Producing Cells Leads to Renal Endothelial Damage

Lachmann¹,

Hickmann²,

Steglich³

et al. 2017

JASN

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Intracellular cAMP, the production of which is catalyzed by the -subunit of the stimulatory G protein (Gs), controls renin synthesis and release by juxtaglomerular (JG) cells of the kidney, but may also have relevance for the physiologic integrity of the kidney. To investigate this possibility, we generated mice with inducible knockout of Gs in JG cells and monitored them for 6 months after induction at 6 weeks of age. The knockout mapped exclusively to the JG cells of the Gs-deficient animals. Progressive albuminuria occurred in Gs-deficient mice. Compared with controls expressing wild-type Gs alleles, the Gs-deficient mice had enlarged glomeruli with mesangial expansion, injury, and FSGS at study end. Ultrastructurally, the glomerular filtration barrier of the Gs-deficient animals featured endothelial gaps, thickened basement membrane, and fibrin-like intraluminal deposits, which are classic signs of thrombotic microangiopathy. Additionally, we found endothelial damage in peritubular capillaries and vasa recta. Because deficiency of vascular endothelial growth factor (VEGF) results in thrombotic microangiopathy, we addressed the possibility that Gs knockout may result in impaired VEGF production. We detected VEGF expression in JG cells of control mice, and cAMP agonists regulated VEGF expression in cultured renin-producing cells. Our data demonstrate that Gs deficiency in JG cells of adult mice results in kidney injury, and suggest that JG cells are critically involved in the maintenance and protection of the renal microvascular endothelium.

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“…reporter [8], highlighting that Cre in the Pdgfrb-CreRha which was "leaky" in combination with Ai14 may have no background activity with a different reporter line [31,32]. Thus, for each CreERT2/loxP system the inclusion of oil-treated controls that carry both the CreERT2 and the reporter allele, is a necessity.…”

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confidence: 99%

Retina-specific targeting of pericytes reveals structural diversity and enables control of capillary blood flow

Ivanova

Corona

Eleftheriou

et al. 2020

Preprint

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Pericytes are a unique class of mural cells essential for angiogenesis, maintenance of the vasculature and are key players in microvascular pathology. However, their diversity and specific roles are poorly understood, limiting our insight into vascular physiology and the ability to develop effective therapies. Here, in the mouse retina, a tractable model of the CNS, we evaluated distinct classes of mural cells along the vascular tree for both structural characterization and physiological manipulation of blood flow. To accomplish this, we first tested three inducible mural cell-specific mouse lines using a sensitive Ai14 reporter and tamoxifen application either by a systemic injection, or by local administration in the form of eye drops. Across three lines, under either the PDGFRb or NG2 promoter, the specificity and pattern of Cre activation varied significantly. In particular, a mouse line with Cre under the NG2 promoter resulted in sparse TdTomato labeling of mural cells, allowing for an unambiguous characterization of anatomical features of individual sphincter cells and capillary pericytes.Furthermore, in one PDGFRb line, we found that focal eye drop application of tamoxifen led to an exclusive Cre-activation in pericytes, without affecting arterial mural cells. We then used this approach to boost capillary blood flow by selective expression of Halorhodopsin, a highly precise hyperpolarizing optogenetic actuator. The ability to exclusively target capillary pericytes may prove a precise and potentially powerful tool to treat microcirculation deficit, a common pathology in numerous diseases. *

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Inducible glomerular erythropoietin production in the adult kidney

Cited by 63 publications

References 74 publications

Distinct signatures of calcium activity in brain pericytes

Distinct signatures of calcium activity in brain pericytes

Interference with Gsα-Coupled Receptor Signaling in Renin-Producing Cells Leads to Renal Endothelial Damage

Retina-specific targeting of pericytes reveals structural diversity and enables control of capillary blood flow

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