The Role of the Podocyte in Preeclampsia

Garovic, Vesna D.

doi:10.2215/cjn.05940614

Cited by 52 publications

(37 citation statements)

References 26 publications

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“…The reasons are not fully understood; podocyte loss is a hallmark of PE, suggesting permanent glomerular damage [25]. Endotheliosis, associated with PE, but also found in normal pregnancies, may herald glomerulosclerosis; tubular and vascular damage may coexist [26, 27].…”

Section: Pregnancy Pe Pregnancy-induced Hypertensive Disorders Andmentioning

confidence: 99%

What We Do and Do Not Know about Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Women’s Day

et al. 2018

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Chronic kidney disease affects approximately 10% of the world’s adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women’s health and specifically their kidney health, on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world’s population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to have an impact on women, with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

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Section: Pregnancy Pe Pregnancy-induced Hypertensive Disorders Andmentioning

confidence: 99%

What We Do and Do Not Know about Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Women’s Day

et al. 2018

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“…As an important structure of glomerular filtration membranes, podocytes play an important role in proteinuria. There is growing evidence, identified by us and others, that podocyte injury is involved in the generation of proteinuria in PE [25][26][27]. AngII can induce podocyte injury via binding to AngII receptor [28]; however, our previous study showed that the expression of AngII and AT1 receptor in the kidney were decreased in a PE rat model.…”

Section: Discussionmentioning

confidence: 71%

Angiotensin II Type I Receptor Agonistic Autoantibody Induces Podocyte Injury via Activation of the TRPC6- Calcium/Calcineurin Pathway in Pre-Eclampsia

Zhang

et al. 2018

Kidney Blood Press Res

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Background/Aims: Angiotensin II type I receptor agonistic autoantibody (AT1-AA) is closely related to pre-eclampsia, which is characterized by proteinuria and hypertension. AT1-AA has been shown to enhance the effect of AngII in pre-eclampsia, such as production of endothelin-1, activation of ROS, and vasoconstriction, which are considered to be associated with hypertension; however, whether or not AT1-AA participates in podocyte damage leading to the generation of proteinuria has not been reported. In this study we investigated the role of pre-eclamptic serum AT1-AA on podocytes and the mechanism underlying the generation of proteinuria. Methods: The levels of AT1-AA isolated from pre-eclamptic sera were determined by an enzyme-linked immunosorbent assay. Human podocytes were cultured in vitro and treated with various concentrations of AT1-AA. Whether or not an ERK1/2 inhibitor and TRPC6 siRNA inhibit the effect of AT1-AA on podocytes was determined. Western blot was used to detect the expression of podocyte-specific proteins (nephrin, synaptopodin, and podocin) and the phosphorylation of ERK1/2 and TRPC6. The arrangement of F-actin was observed by immunofluorescence. A Calcineurin Cellular Activity Assay Kit was used to detect calcineurin activity. Changes in the intracellular Ca²⁺ concentration was determined by confocal laser. Results: AT1-AA induced a decrease in podocyte-specific protein expression and calcineurin activity and increased expression of p-ERK1/2 and TRPC6 protein and the intracellular Ca²⁺ concentration. Immunofluorescence revealed rearrangement of F-actin. PD98059, an inhibitor of ERK1/2, and TRPC6 siRNA attenuated the decreased expression of podocyte-specific proteins and decreased intracellular Ca²⁺ concentration. The expression of TRPC6 was reduced following the addition of ERK1/2 inhibitor. Conclusion: AT1-AA induced podocyte damage in a dose-dependent manner. The underlying mechanism might involve activation of the TRPC6 –calcium/calcineurin pathway. This study provides new details regarding podocyte injury and the mechanism underlying the generation of proteinuria in pre-eclampsia.

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“…PE is a risk factor for the future development of CKD and ESRD in the mother [3][4][5]. The reasons are not fully understood; podocyte loss is a hallmark of PE, suggesting permanent glomerular damage [25]. Endotheliosis, associated with PE, but also found in normal pregnancies, may herald glomerulosclerosis; tubular and vascular damage may co-exist [26,27].…”

Section: What We Knowmentioning

confidence: 99%

What we do and do not know about women and kidney diseases; questions unanswered and answers unquestioned: reflection on World Kidney Day and International Women’s Day

et al. 2018

View full text Add to dashboard Cite

Chronic Kidney Disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

show abstract

The Role of the Podocyte in Preeclampsia

Cited by 52 publications

References 26 publications

What We Do and Do Not Know about Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Women’s Day

What We Do and Do Not Know about Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Women’s Day

Angiotensin II Type I Receptor Agonistic Autoantibody Induces Podocyte Injury via Activation of the TRPC6- Calcium/Calcineurin Pathway in Pre-Eclampsia

What we do and do not know about women and kidney diseases; questions unanswered and answers unquestioned: reflection on World Kidney Day and International Women’s Day

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