Intravital visualization of the primary cilium, tubule flow, and innate immune cells in the kidney utilizing an abdominal window imaging approach

Revell, Dustin Z.; Yoder, Bradley K.

doi:10.1016/bs.mcb.2019.04.012

Cited by 14 publications

(10 citation statements)

References 40 publications

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“…Similarly, to introduce optogenetics in this system to manipulate or rescue cellular signaling pathways with spatial resolution relies on new technical developments in intravital imaging in the kidney. Although intravital imaging in the kidney is feasible (Revell & Yoder, 2019 ), two‐photon excitation for many optogenetic tools is limited and requires an indirect approach or one‐photon excitation using a light fiber. However, we are confident that novel technical developments in the next few years will allow to apply our optogenetic approach to study PKD development in vivo .…”

Section: Discussionmentioning

confidence: 99%

A cAMP signalosome in primary cilia drives gene expression and kidney cyst formation

et al. 2022

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The primary cilium constitutes an organelle that orchestrates signal transduction independently from the cell body. Dysregulation of this intricate molecular architecture leads to severe human diseases, commonly referred to as ciliopathies. However, the molecular underpinnings how ciliary signaling orchestrates a specific cellular output remain elusive. By combining spatially resolved optogenetics with RNA sequencing and imaging, we reveal a novel cAMP signalosome that is functionally distinct from the cytoplasm. We identify the genes and pathways targeted by the ciliary cAMP signalosome and shed light on the underlying mechanisms and downstream signaling. We reveal that chronic stimulation of the ciliary cAMP signalosome transforms kidney epithelia from tubules into cysts. Counteracting this chronic cAMP elevation in the cilium by small molecules targeting activation of phosphodiesterase‐4 long isoforms inhibits cyst growth. Thereby, we identify a novel concept of how the primary cilium controls cellular functions and maintains tissue integrity in a specific and spatially distinct manner and reveal novel molecular components that might be involved in the development of one of the most common genetic diseases, polycystic kidney disease.

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Section: Discussionmentioning

confidence: 99%

A cAMP signalosome in primary cilia drives gene expression and kidney cyst formation

et al. 2022

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“…However, the conventional research method of lineage tracing relying on sacrificing the animals to get the information on the tissue sections is only a "snapshot" (19,22), which is unable to dynamically monitor the Sox9 1 cell behavior in action. The abdominal imaging window (AIW) successfully solves this problem, making researchers able to visualize as well as quantify the cell fate and reparative process by lineage tracing in real-time, in vivo in an individual mouse (23)(24)(25). In addition, the application of two-photon microscopy (TPM) improves the feasibility of lineage tracing by living imaging at a single-cell level because of its advantages, such as deep tissue penetration and little photodamage (22).…”

mentioning

confidence: 99%

In vivo two-photon microscopy reveals the contribution of Sox9+ cell to kidney regeneration in a mouse model with extracellular vesicle treatment

Zhang

Shang

Sun

et al. 2020

Journal of Biological Chemistry

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Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been shown to stimulate regeneration in the treatment of kidney injury. Renal regeneration is also thought to be stimulated by the activation of Sox9+ cells. However, whether and how the activation mechanisms underlying EV treatment and Sox9+ cell-dependent regeneration intersect is unclear. We reasoned that a high-resolution imaging platform in living animals could help to untangle this system. To test this idea, we first applied EVs derived from human placenta-derived MSCs (hP-MSCs) to a Sox9-CreERT2; R26mTmG transgenic mouse model of acute kidney injury (AKI). Then, we developed an abdominal imaging window (AIW) in the mouse and tracked the Sox9+ cells in the inducible Sox9 Cre transgenic mice via in vivo lineage tracing with two-photon intravital microscopy. Our results demonstrated that EVs can travel to the injured kidneys post intravenous injection as visualized by Gaussia luciferase imaging and markedly increased the activation of Sox9+ cells. Moreover, the two-photon living imaging of lineage-labeled Sox9+ cells showed that the EVs promoted the expansion of Sox9+ cells in kidneys post AKI. Histological staining results confirmed that the descendants of Sox9+ cells contributed to nephric tubule regeneration which significantly ameliorated the renal function after AKI. In summary, intravital lineage tracing with two-photon microscopy through an embedded AIW provides a practical strategy to investigate the beneficial functions and to clarify the mechanisms of regenerative therapies in AKI.

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“…Recently, an intra vital technique to visualize renal cilia in a live mouse showed that under normal conditions, the tubule luminal cilia do not oscillate but rather remain bent flat against the tubule wall [99]. This suggests that, at least in mice, cilia are typically subjected to maximum deflection.…”

Section: Signal Transduction By the Polycystin Complexmentioning

confidence: 99%

c-JUN n-Terminal Kinase (JNK) Signaling in Autosomal Dominant Polycystic Kidney Disease

Smith

Jonassen

Preval

et al. 2022

Journal of Cellular Signaling

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Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder characterized by slow-growing, fluid-filled cysts in both kidneys. Liver and pancreatic cysts as well as cardiac and vascular abnormalities variably occur [1,2]. ADPKD symptoms include hypertension, kidney pain, hematuria, cyst infection, and urinary tract infections [1]. Over time, deteriorating kidney function leads to end stage renal disease (ESRD). While most ADPKD patients progress to ESRD by age 70, many reach it at younger ages [3]. Despite recent advances in therapy, ADPKD remains incurable, and for most patients treatment is limited to symptom management [4]. For patients with ESRD, renal replacement therapy in the form of dialysis or transplant is inevitable. Unfortunately, renal transplantation does not cure ESRD and patients commonly experience acute rejection, cardiovascular diseases, infection, and malignancy [5].

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Intravital visualization of the primary cilium, tubule flow, and innate immune cells in the kidney utilizing an abdominal window imaging approach

Cited by 14 publications

References 40 publications

A cAMP signalosome in primary cilia drives gene expression and kidney cyst formation

A cAMP signalosome in primary cilia drives gene expression and kidney cyst formation

In vivo two-photon microscopy reveals the contribution of Sox9+ cell to kidney regeneration in a mouse model with extracellular vesicle treatment

c-JUN n-Terminal Kinase (JNK) Signaling in Autosomal Dominant Polycystic Kidney Disease

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