Tenascins and osteopontin in biological response in cornea

Sumioka, Takayoshi; Matsumoto, K.; Reinach, Peter S.; Saika, Shizuya

doi:10.1016/j.jtos.2023.05.005

Cited by 2 publications

(2 citation statements)

References 217 publications

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“…The binding of OPN with integrins initiates the activation of several downstream signaling effectors, such as phosphatidylinositol 3 kinase (PI3K) /protein kinase B (AKT), focal adhesion kinase (FAK)/AKT and nuclear factor kappa-B (NF-κB), leading to cell proliferation, migration, epithelial–mesenchymal transition (EMT), inflammation, neurotoxic microglial phenotype, tumor growth, migration and invasion, as well as angiogenesis within the chronic subdural hematoma (CSDH) outer membrane [ 15 , 16 , 17 , 18 , 19 , 20 ]. In addition, OPN regulates other signal pathways or signal molecules, such as Janus kinase (JAK)/signal transducer and activator of transcription (STAT) [ 21 , 22 , 23 , 24 ], PI3K/AKT [ 15 , 25 , 26 , 27 ], NOTCH [ 28 , 29 ], extracellular regulated protein kinase1/2 (ERK1/2) [ 30 ], the ubiquitin C -terminal hydrolase L1 (UCHL1)–ubiquitin–proteasome system (UPS) axis [ 31 ] and transforming growth factor β (TGF-β) [ 32 ], influencing cellular physiological processes and disease progression. OPN also acts as a ligand for CD44 that results in attracting mesenchymal stem cells (MSCs) to the tumor microenvironment, promoting EMT and tumor budding (TB), inducing macrophage migration and activation, stimulating intestinal growth, differentiation and maturation, cell growth, proliferation, migration and cell-cycle activity and promoting oxidative stress [ 15 , 17 , 23 , 33 , 34 , 35 , 36 ].…”

Section: Functions Of Opnmentioning

confidence: 99%

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Immunoregulatory Roles of Osteopontin in Diseases

Wang,

Niu

2024

Nutrients

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Osteopontin (OPN) is a multifunctional protein that plays a pivotal role in the immune system. It is involved in various biological processes, including cell adhesion, migration and survival. The study of the immunomodulatory effects of OPN is of paramount importance due to its potential therapeutic applications. A comprehensive understanding of how OPN regulates the immune response could pave the way for the development of novel treatments for a multitude of diseases, including autoimmune disorders, infectious diseases and cancer. Therefore, in the following paper, we provide a systematic overview of OPN and its immunoregulatory roles in various diseases, laying the foundation for the development of OPN-based therapies in the future.

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Section: Functions Of Opnmentioning

confidence: 99%

“…It inhibits TGFβ signaling in corneal stromal cells, thus protecting corneal transparency and tensile strength, and affects the integrity and function of the corneal endothelial layer. The modulation of their functions could be a novel strategy to improve the outcome of corneal wound healing [ 32 ].…”

Section: Immunoregulatory Roles Of Opn In Diseasesmentioning

confidence: 99%

Immunoregulatory Roles of Osteopontin in Diseases

Wang,

Niu

2024

Nutrients

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Corneal keratocytes, fibroblasts, and myofibroblasts exhibit distinct transcriptional profilesin vitro

Poole,

Iyer,

Schmidtke

et al. 2024

Preprint

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After a stromal injury in the cornea, the release of growth factors and pro-inflammatory cytokines typically results in the activation of quiescent keratocytes toward migratory fibroblast and/or fibrotic myofibroblast phenotypes. The persistence of the myofibroblast phenotype can lead to corneal fibrosis and scarring, which are leading causes of blindness worldwide. The primary goal of this study was to establish comprehensive transcriptional profiles for cultured corneal keratocytes, fibroblasts, and myofibroblasts to gain insights into the mechanisms through which changes in phenotype may occur. Here, we cultured primary rabbit corneal keratocytes on collagen-coated glass coverslips in serum free media (SF), serum containing media (FBS), or in the presence of TGF-β1 to induce keratocyte, fibroblast, and myofibroblast phenotypes, respectively. Total RNA was collected and sent to Novogene for bulk RNA sequencing. Subsequent bioinformatic analysis included gene expression quantification, differential expression, and functional analysis. When comparing FBS and TGF-β1 conditions to SF, genes characteristic of a quiescent keratocyte phenotype were downregulated (e.g. KERA, LUM, ALDH1A1), while genes commonly associated with fibroblasts or myofibroblasts were upregulated (e.g. VIM, TNC, FN1, ITGA5, ACTA2). Functional analysis of genes differentially expressed between fibroblasts and keratocytes highlighted pathways related to proliferation (e.g. DNA replication, PI3K-Akt signaling) and cell migration (e.g. Rap1 signaling, ECM-receptor interactions). Enriched pathways for the comparison of myofibroblasts to keratocytes included focal adhesion, regulation of actin cytoskeleton, hippo signaling, and ECM-receptor interaction pathways. Together, these pathways support changes in cytoskeletal organization, cell contractility, mechanotransduction, and cell-ECM interactions in myofibroblasts compared to keratocytes. Overall, these data demonstrate that there are distinct transcriptional differences between cultured corneal keratocytes, fibroblasts, and myofibroblasts. In our initial analysis, we have identified genes and signaling pathways that may play important roles in keratocyte differentiation, including many related to proliferation, cell mechanical activity, and ECM interactions. Furthermore, our findings reveal novel markers for each cell type as well as possible targets for modulating cell behavior and differentiation to promote physiological corneal wound healing.

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Tenascins and osteopontin in biological response in cornea

Cited by 2 publications

References 217 publications

Immunoregulatory Roles of Osteopontin in Diseases

Immunoregulatory Roles of Osteopontin in Diseases

Corneal keratocytes, fibroblasts, and myofibroblasts exhibit distinct transcriptional profilesin vitro

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