Role of the Hippo pathway in autoimmune diseases

Kong, Hui; Han, Juan-Juan; Gorbachev, Dmitrii; Zhang, Xin-An

doi:10.1016/j.exger.2023.112336

Cited by 3 publications

(3 citation statements)

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“…In terms of AR-EAE incidence ( Eaecc3) , Yap1/YAP1, which is a key component of the Hippo signaling pathway 85 , and Dync2h1/DYNC2H1 , which encodes a dynein motor protein that has been shown to be involved in intraciliary transport, were the top prioritized genes for Eaecc3 for the immune system and CNS networks, respectively. Recent studies have suggested the involvement of the Hippo signaling pathway in autoimmune pathogenesis, with emphasis on the balance between T regulatory cell (Treg) and pro-inflammatory Th17 cell differentiation through Yap - Taz expression 85 , as well as specific evidence for involvement in RA, inflammatory bowel disease, and psoriasis 86 , all of which have been shown to have genetic overlap with MS 82,83 . In contrast, less direct evidence for involvement in EAE/MS pathogenesis exists for Dync2h1/DYNC2H1 .…”

Section: Discussionmentioning

confidence: 99%

Probing the basis of disease heterogeneity in multiple sclerosis using genetically diverse mice

Holt,

Tyler,

Lakusta-Wong

et al. 2024

Preprint

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Multiple sclerosis (MS) is a complex disease with significant heterogeneity in disease course and progression. Genetic studies have identified numerous loci associated with MS risk, but the genetic basis of disease progression remains elusive. To address this, we leveraged the Collaborative Cross (CC), a genetically diverse mouse strain panel, and experimental autoimmune encephalomyelitis (EAE). The thirty-two CC strains studied captured a wide spectrum of EAE severity, trajectory, and presentation, including severe-progressive, monophasic, relapsing remitting, and axial rotary (AR)-EAE, accompanied by distinct immunopathology. Sex differences in EAE severity were observed in six strains. Quantitative trait locus analysis revealed distinct genetic linkage patterns for different EAE phenotypes, including EAE severity and incidence of AR-EAE. Machine learning-based approaches prioritized candidate genes for loci underlying EAE severity (Abcc4andGpc6) and AR-EAE (Yap1andDync2h1). This work expands the EAE phenotypic repertoire and identifies novel loci controlling unique EAE phenotypes, supporting the hypothesis that heterogeneity in MS disease course is driven by genetic variation.SummaryThe genetic basis of disease heterogeneity in multiple sclerosis (MS) remains elusive. We leveraged the Collaborative Cross to expand the phenotypic repertoire of the experimental autoimmune encephalomyelitis (EAE) model of MS and identify loci controlling EAE severity, trajectory, and presentation.

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Section: Discussionmentioning

confidence: 99%

Probing the basis of disease heterogeneity in multiple sclerosis using genetically diverse mice

Holt,

Tyler,

Lakusta-Wong

et al. 2024

Preprint

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“…35 The effect of the Hippo-YAP signaling pathway is mainly focused on regulating embryonic development, cell apoptosis, differentiation and organ growth. 36 Hippo-YAP was first discovered due to its critical role in regulating organ size and is highly conserved among mammals. 36 Because of its influence on tissue growth and organ size, the Hippo-YAP signaling pathway has been extensively studied in oncology and other diseases.…”

Section: A Brief History Of the Hippo Signaling Pathwaymentioning

confidence: 99%

“…36 Hippo-YAP was first discovered due to its critical role in regulating organ size and is highly conserved among mammals. 36 Because of its influence on tissue growth and organ size, the Hippo-YAP signaling pathway has been extensively studied in oncology and other diseases. Previous studies have shown that low YAP/TAZ mRNA levels are related to the severity of cancer, especially in myeloma, lymphoma and leukemia, which at least in part https://doi.org/10.2147/JIR.S444758…”

Section: A Brief History Of the Hippo Signaling Pathwaymentioning

confidence: 99%

The Hippo-YAP Signaling Pathway in Osteoarthritis and Rheumatoid Arthritis

Li,

Zhang,

Bai

2024

JIR

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Arthritis is the most prevalent joint disease and is characterized by articular cartilage degradation, synovial inflammation, and changes in periarticular and subchondral bone. Recent studies have reported that Yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) have significant effects on the proliferation, migration, and survival of chondrocytes and fibroblast-like synovial cells (FLSs). YAP/TAZ signaling pathway, as well as the related Hippo-YAP signaling pathway, are responsible for the condition of cells and articular cartilage in joints. They are tightly regulated to maintain metabolism in chondrocytes and FLSs because abnormal expression may result in cartilage damage. However, the roles and mechanisms of the Hippo-YAP pathway in arthritis remain largely unknown. This review summarizes the roles and key functions of YAP/TAZ and the Hippo-YAP signaling pathway in FLSs and chondrocytes for the induction of proliferation, migration, survival, and differentiation in rheumatoid arthritis (RA) and osteoarthritis (OA) research. We also discuss the therapeutic strategies involving YAP/TAZ and the related Hippo-YAP signaling pathway involved in OA.

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