Effect of hepatocytic RKIP depletion on HFD-induced MASLD
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ABSTRACT:
PROVIDER: PRJNA1279072 | ENA |
REPOSITORIES: ENA
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Project description:High-fat diet (HFD) is a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), yet the molecular pathways that connect dietary fats to liver dysfunction remain unclear. Hepatocyte-specific RKIP depletion in male mice exacerbates ER stress, resulting in lipid droplets accumulation and MASLD progression.
2025-09-03 | GSE300123 | GEO
Project description:Tracking development and progression of MASLD using ALIOS diet intervention in mice at 8,12, and 16 weeks.
2025-10-01 | MSV000099345 | MassIVE
Project description:The burden of senescent hepatocytes correlates with MASLD severity but mechanisms driving senescence, and how it exacerbates MASLD are poorly understood. Hepatocytes become senescent when Smoothened (Smo) is deleted to disrupt Hedgehog signaling. We aimed to determine if the secretomes of Smo-deficient hepatocytes perpetuate senescence to drive MASLD progression. RNA seq analysis confirmed that hepatocyte populations of MASLD livers are depleted of Smo(+) cells and enriched with senescent cells. When fed CDA-HFD, Smo(-) mice had lower antioxidant markers and developed worse DNA damage, senescence, MASH and liver fibrosis than Smo(+) mice. Sera and hepatocyte-conditioned medium from Smo(-) mice were depleted of thymidine phosphorylase (TP), a protein that maintains mitochondrial fitness. Treating Smo(-) hepatocytes with TP reduced senescence and lipotoxicity; inhibiting TP in Smo(+) hepatocytes had the opposite effects and exacerbated hepatocyte senescence, MASH, and fibrosis in CDA-HFD-fed mice.Therefore, we found that inhibiting Hedgehog signaling in hepatocytes promotes MASLD by suppressing hepatocyte production of proteins that prevent lipotoxicity and senescence.
2024-10-01 | GSE273523 | GEO
Project description:RKIP has been implicated in suppression of breast tumor metastasis. Identification of microRNAs regulated by RKIP helps us to understand how RKIP suppresses tumor metastasis via its downstream target mircoRNAs and genes. Total RNA was extracted from 1833 cells expressing RKIP or control, respectively. Exiqon miRCURY LNA array v.11.0. was performed to identify the microRNAs regulated by RKIP.
2014-07-01 | E-GEOD-47366 | biostudies-arrayexpress
Project description:RKIP regulates human breast tumor metastasis. We use gene expression array analysis to identify genes regulated by RKIP in human breast cancer cells. Total RNAs were extracted from 1833 cells expressing mutant RKIP (S153E-RKIP, a more potent Raf-1 inhibitor) and vector control. Affymetrix GeneChip hgu133plus2.0 Arrays were performed to detail the gene expression and identify the genes regulated by RKIP in human breast cancer cells.
2014-07-01 | E-GEOD-47378 | biostudies-arrayexpress
Project description:Raf Kinase Inhibitor Protein (RKIP) has been extensively reported as an inhibitor of key signaling pathways involved in the aggressive tumor phenotype and shows decreased expression in several types of cancers. However, little is known about RKIP in melanoma or regarding its function in normal cells. We examined the role of RKIP in both primary melanocytes and malignant melanoma cells and evaluated its diagnostic and prognostic value. IHC analysis revealed a significantly higher expression of RKIP in nevi compared with early-stage (stage I-II, AJCC 8th) melanoma biopsies. Proliferation, wound healing, and collagen-coated transwell assays uncovered the implication of RKIP on the motility but not on the proliferative capacity of melanoma cells as RKIP protein levels were inversely correlated with the migration capacity of both primary and metastatic melanoma cells but did not alter other parameters. As shown by RNA sequencing, endogenous RKIP knockdown in primary melanocytes triggered the deregulation of cellular differentiation-related processes, including genes (i.e., ZEB1, THY-1) closely related to the EMT. Interestingly, NANOG was identified as a putative transcriptional regulator of many of the deregulated genes, and RKIP was able to decrease the activation of the NANOG promoter. As a whole, our data support the utility of RKIP as a diagnostic marker for early-stage melanomas. In addition, these findings indicate its participation in the maintenance of a differentiated state of melanocytic cells by modulating genes intimately linked to the cellular motility and explain the progressive decrease of RKIP often described in tumors.
2020-07-01 | GSE151585 | GEO
Project description:RKIP has been implicated in suppression of breast tumor metastasis. Identification of microRNAs regulated by RKIP helps us to understand how RKIP suppresses tumor metastasis via its downstream target mircoRNAs and genes.
2014-07-01 | GSE47366 | GEO
Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with obesity. The use of animal models fed Western-style diets is vital for investigating the molecular mechanisms contributing to metabolic dysregulation and for facilitating novel drug target identification. However, the sex- and age-associated mechanisms underlying the pathophysiology remain poorly understood. Here we show distinct responses to a HFD between males and females. Our study underscores the need for utilizing both sexes in drug target identification studies, and characterizing the molecular mechanisms contributing to the MASLD pathophysiology in aging animals. Hepatology Communications 2024
2024-09-03 | GSE274914 | GEO
Project description:RKIP regulates human breast tumor metastasis. We use gene expression array analysis to identify genes regulated by RKIP in human breast cancer cells.
2014-07-01 | GSE47378 | GEO
Project description:Raf-1 kinase inhibitor protein (RKIP = PEBP1) has been shown to negatively regulate signaling pathways including the MAPK and NFkappaB pathways involved in cancer progression and metastasis. RKIP acts as a suppressor of metastasis, but the exact mechanisms are unclear. In this study, knockdown of RKIP expression was used to identify the targets of RKIP expression. GSEA analysis identified interferon response genes as downregulated in the RKIP knockdown cells.
2022-07-21 | GSE206259 | GEO