Estrogen-induced signalling and the renal contribution to salt and water homeostasis

Thomas, Warren; Harvey, Brian J.

doi:10.1016/j.steroids.2023.109299

Cited by 4 publications

(4 citation statements)

References 91 publications

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“…Figure 1 illustrates the independence of the three types of expression characteristics for 37 genes involved in the KEGG-constructed pathway of the "Endocrine and other factor-regulated calcium reabsorption" [59] using our microarray data on Fuhrman grade 3 metastatic ccRCC samples [38]. For the COR analysis, we chose to represent the expression correlation with the estrogen receptor 1 (ESR1), owing to the kidney being one of "the most estrogen-responsive, not reproductive organs in the body" [62].…”

Section: Independent Characteristics Of Gene Expressionmentioning

confidence: 99%

Genomic Fabrics of the Excretory System’s Functional Pathways Remodeled in Clear Cell Renal Cell Carcinoma

Iacobas,

Obiomon,

Iacobas

2023

CIMB

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Clear cell renal cell carcinoma (ccRCC) is the most frequent form of kidney cancer. Metastatic stages of ccRCC reduce the five-year survival rate to 15%. In this report, we analyze the ccRCC-induced remodeling of the five KEGG-constructed excretory functional pathways in a surgically removed right kidney and its metastasis in the chest wall from the perspective of the Genomic Fabric Paradigm (GFP). The GFP characterizes every single gene in each region by these independent variables: the average expression level (AVE), relative expression variability (REV), and expression correlation (COR) with each other gene. While the traditional approach is limited to only AVE analysis, the novel REV analysis identifies the genes whose correct expression level is critical for cell survival and proliferation. The COR analysis determines the real gene networks responsible for functional pathways. The analyses covered the pathways for aldosterone-regulated sodium reabsorption, collecting duct acid secretion, endocrine and other factor-regulated sodium reabsorption, proximal tubule bicarbonate reclamation, and vasopressin-regulated water reabsorption. The present study confirms the conclusion of our previously published articles on prostate and kidney cancers that even equally graded cancer nodules from the same tumor have different transcriptomic topologies. Therefore, the personalization of anti-cancer therapy should go beyond the individual, to his/her major cancer nodules.

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Section: Independent Characteristics Of Gene Expressionmentioning

confidence: 99%

Genomic Fabrics of the Excretory System’s Functional Pathways Remodeled in Clear Cell Renal Cell Carcinoma

Iacobas,

Obiomon,

Iacobas

2023

CIMB

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“…We found similar protection with another AQP4 inhibitor, TGN-020, which has not yet been tested with this assay. We also found that female mice were protected from mortality after WI, which may be due to increased estrogen signaling in the kidney endowing female mice with a greater capacity to buffer the osmotic challenge (Thomas & Harvey, 2023). Importantly, AER-271 was only protective when given prior to the osmotic challenge, likely because the pro-drug needs time to be converted into the active form to be effective.…”

Section: Discussionmentioning

confidence: 78%

“…To our knowledge, this paradigm has previously been used with only male mice, and it could be females have a greater capacity to buffer the osmotic challenge via estrogen signaling in the kidney (Thomas & Harvey, 2023).…”

Section: Aer-271 Is Protective From Hyponatremia Induced Brain Swellingmentioning

confidence: 99%

Glymphatic fluid transport is suppressed by the aquaporin‐4 inhibitor AER‐271

Giannetto,

Gomolka,

Gahn‐Martinez

et al. 2024

Glia

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The glymphatic system transports cerebrospinal fluid (CSF) into the brain via arterial perivascular spaces and removes interstitial fluid from the brain along perivenous spaces and white matter tracts. This directional fluid flow supports the clearance of metabolic wastes produced by the brain. Glymphatic fluid transport is facilitated by aquaporin‐4 (AQP4) water channels, which are enriched in the astrocytic vascular endfeet comprising the outer boundary of the perivascular space. Yet, prior studies of AQP4 function have relied on genetic models, or correlated altered AQP4 expression with glymphatic flow in disease states. Herein, we sought to pharmacologically manipulate AQP4 function with the inhibitor AER‐271 to assess the contribution of AQP4 to glymphatic fluid transport in mouse brain. Administration of AER‐271 inhibited glymphatic influx as measured by CSF tracer infused into the cisterna magna and inhibited increases in the interstitial fluid volume as measured by diffusion‐weighted MRI. Furthermore, AER‐271 inhibited glymphatic efflux as assessed by an in vivo clearance assay. Importantly, AER‐271 did not affect AQP4 localization to the astrocytic endfeet, nor have any effect in AQP4 deficient mice. Since acute pharmacological inhibition of AQP4 directly decreased glymphatic flow in wild‐type but not in AQP4 deficient mice, we foresee AER‐271 as a new tool for manipulation of the glymphatic system in rodent brain.

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“…30,31 Previous research has demonstrated the impact of estrogen on the growth of TSC2 deficient cells as well as the development of renal angiomyolipoma associated with TSC. 32,33 Thus, the differences in waitlisting may reflect sexbased hormonal differences-specifically the role of estrogen signaling in the kidney 34 among TSC patients, leading to potentially more severe renal disease among women with TSC.…”

Section: Discussionmentioning

confidence: 99%

Kidney transplantation in patients with tuberous sclerosis complex

Goedken,

Ismail,

Barrett

et al. 2024

Pediatric Transplantation

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BackgroundTuberous sclerosis complex (TSC) is a disorder of the mammalian target of the rapamycin (mTOR) pathway associated with the development of multisystem tumors, including renal angiomyolipoma (AML). These renal tumors are benign by nature but locally invasive and carry a risk for the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). The frequency of subsequent renal transplantation in this population is largely uncharacterized, although single‐center data suggests that 5%–15% of adult TSC patients are kidney transplant recipients.MethodsThis retrospective cohort study utilized United Network for Organ Sharing (UNOS) data. We included candidates waitlisted between 1987 and 2020 for a first kidney transplant with TSC‐associated kidney failure. We utilized descriptive statistics to characterize the frequency of first‐time kidney transplant waitlisting and transplantation among persons with TSC and the Fine‐Gray subdistribution hazard model to evaluate characteristics associated with progression from waitlist.ResultsWe identified 200 TSC‐associated kidney failure patients within the waitlist cohort. Of these, 12 were pediatric patients. Two‐thirds (N = 134) of waitlisted persons were female. One hundred forty patients received a transplant with a median waitlist time of 2 years. Younger age at waitlisting was associated with a greater probability of progressing to transplant (HR 0.98 [95% CI: 0.96–0.99]). 91.8% of kidney transplant recipients survived 1‐year post‐transplant with a functioning allograft.ConclusionsThe majority of patients with TSC who are waitlisted for a kidney transplant progress onto transplantation with excellent 1‐year post transplant patient and allograft survival.

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Estrogen-induced signalling and the renal contribution to salt and water homeostasis

Cited by 4 publications

References 91 publications

Genomic Fabrics of the Excretory System’s Functional Pathways Remodeled in Clear Cell Renal Cell Carcinoma

Genomic Fabrics of the Excretory System’s Functional Pathways Remodeled in Clear Cell Renal Cell Carcinoma

Glymphatic fluid transport is suppressed by the aquaporin‐4 inhibitor AER‐271

Kidney transplantation in patients with tuberous sclerosis complex

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