Calcineurin in development and disease

Chen, Lei; Song, Min; Yao, Chunyan

doi:10.1016/j.gendis.2021.03.002

Cited by 30 publications

(13 citation statements)

References 146 publications

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“…Further studies are required to understand how inflammatory factors like C3 and NINJ1 coordinate immune reactions in the vicinity of Aβ plaques. The calmodulin-dependent serine/threonine protein phosphatase PPP3CA (calcineurin), the deubiquitinating enzyme UCHL1, and the neuropeptide SST are all implicated in AD (85,(113)(114)(115). Aβ plaques appear to be enriched near cells expressing these DEGs, but their density decreases with distance from these cells.…”

Section: Discussionmentioning

confidence: 99%

Influence of Alzheimer’s disease related neuropathology on local microenvironment gene expression in the human inferior temporal cortex

Kwon

Parthiban

Tippani

et al. 2023

Preprint

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Neuropathological lesions in the brains of individuals affected with neurodegenerative disorders are hypothesized to trigger molecular and cellular processes that disturb homeostasis of local microenvironments. Here, we applied the 10x Genomics Visium Spatial Proteogenomics (Visium-SPG) platform, which measures spatial gene expression coupled with immunofluorescence protein co-detection, in post-mortem human brain tissue from individuals with late-stage Alzheimer's disease (AD) to investigate changes in spatial gene expression with respect to amyloid-β (Aβ) and hyperphosphorylated tau (pTau) pathology. We identified Aβ-associated transcriptomic signatures in the human inferior temporal cortex (ITC) during late-stage AD, which we further investigated at cellular resolution with combined immunofluorescence and single molecule fluorescent in situ hybridization (smFISH) co-detection technology. We present a workflow for analysis of Visium-SPG data and demonstrate the power of multi-omic profiling to identify spatially-localized changes in molecular dynamics that are linked to pathology in human brain disease. We provide the scientific community with web-based, interactive resources to access the datasets of the spatially resolved AD-related transcriptomes at https://research.libd.org/Visium_SPG_AD/.

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Section: Discussionmentioning

confidence: 99%

Influence of Alzheimer’s disease related neuropathology on local microenvironment gene expression in the human inferior temporal cortex

Kwon

Parthiban

Tippani

et al. 2023

Preprint

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“…Upon the activation of the hypertrophic response, calcineurin activated by the presence of elevated cytosolic calcium concentration promotes dephosphorylation of p-NFATC3 and other transcription factors. NFATC3 forms a complex with GATA4, which then activates downstream transcription factors and fetal genes, such as BNP and ANP [ 39 , 41 ]. Treatment with the ethyl acetate fraction inhibited the increase in the expression of calcineurin, NFATC3, and p-GATA4 induced by Ang II, indicating that its cardioprotective activity may occur in part via a calcineurin-related pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Physiologically, calcineurin participates in various cellular processes, including immunomodulation and cardiomyocyte maturation. However, pathologically, the activation of NFAT by calcineurin induces the activation of T cells and tumor necrosis factor α in addition to hypertrophic gene transcription, leading to pathological hypertrophy and initiation of the inflammatory process in cardiomyocytes [ 41 ]. Therefore, it can be hypothesized that the fraction inhibited the development of the inflammatory process and subsequently inhibited hypertrophic events.…”

Section: Discussionmentioning

confidence: 99%

Parkia speciosa Hassk. Empty Pod Extract Prevents Cardiomyocyte Hypertrophy by Inhibiting MAPK and Calcineurin-NFATC3 Signaling Pathways

Mustafa

Jalil

Saleh

et al. 2022

Life

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Cardiac hypertrophy is an early hallmark during the clinical course of heart failure. Therapeutic strategies aiming to alleviate cardiac hypertrophy via the mitogen-activated protein kinase (MAPK)/calcineurin-nuclear factor of activated T-cells (NFAT) signaling pathway may help prevent cardiac dysfunction. Previously, empty pod ethanol crude extract of Parkia speciosa Hassk was shown to demonstrate protective effects against cardiomyocyte hypertrophy. Therefore, the current study aimed to investigate the effects of various fractions of the plant ethanol extract on the MAPK/NFAT signaling pathway in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. Simultaneous treatment with ethyl acetate (EA) fraction produced the most potent antihypertrophic effect evidenced by the reduced release of B-type natriuretic peptide (BNP). Subsequently, treatment with the EA fraction (6.25, 12.5, and 25 μg/mL) prevented an Ang II-induced increase in cell surface area, hypertrophic factors (atrial natriuretic peptide and BNP), reactive oxygen species, protein content, and NADPH oxidase 4 expression in the cells. Furthermore, EA treatment attenuated the activation of the MAPK pathway and calcineurin-related pathway (GATA-binding protein 4 and NFATC3), which was similar to the effects of valsartan (positive control). Our findings indicate that the EA fraction prevents Ang II-induced cardiac hypertrophy by regulating the MAPK/calcineurin-NFAT signaling pathway.

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“…The nephrotoxic potential of tacrolimus has been well described. 19 The increased risk of nephrotoxicity and gestational diabetes places patients with a uterus transplant at an increased risk to develop preeclampsia. In this cohort we define nephrotoxicity as a creatinine > 1.0 mg/dL.…”

Section: Blood Pressure and Renal Functionmentioning

confidence: 99%

Antepartum Care of the Uterus Transplant Patient: The Experience of 3 Successful US Centers

Perni

Wang

Gregg

2022

Clinical Obstetrics &Amp; Gynecology

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We offer consensus recommendations for the antepartum management of the uterus transplant pregnancy based on our experience at 3 US centers. Patient access to accurate information is important to manage expectations and make informed decisions. Unique aspects of medical management include monitoring tacrolimus levels and performing cervical biopsies for rejection. Low-dose aspirin for preeclampsia is routinely used. Vigilant screening for gestational diabetes and preeclampsia allows for the prompt diagnosis and treatment of these common complications. We aim to deliver patients at 37 to 38 weeks by cesarean section. Shared decision making dominates whether to consider future pregnancies and timing of hysterectomy.

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Calcineurin in development and disease

Cited by 30 publications

References 146 publications

Influence of Alzheimer’s disease related neuropathology on local microenvironment gene expression in the human inferior temporal cortex

Influence of Alzheimer’s disease related neuropathology on local microenvironment gene expression in the human inferior temporal cortex

Parkia speciosa Hassk. Empty Pod Extract Prevents Cardiomyocyte Hypertrophy by Inhibiting MAPK and Calcineurin-NFATC3 Signaling Pathways

Antepartum Care of the Uterus Transplant Patient: The Experience of 3 Successful US Centers

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