Osteopontin as a candidate of therapeutic application for the acute brain injury

Zhou, Yunxiang; Yao, Yanlai; Sheng, Lesang; Zhang, Jianmin; Zhang, Junyi; Shao, Anwen

doi:10.1111/jcmm.15641

Cited by 29 publications

(41 citation statements)

References 160 publications

(450 reference statements)

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“…For example, OPN expression during early or late stages of inflammatory diseases seems to regulate the production of cytokines with distinct pro-or anti-inflammatory functions (381,382,383). Different isoforms, terminal fragments and posttranscriptional modifications of OPN may yield different impact as described in acute brain injury (384,385,386). Finally, OPN binds to multiple integrins and other receptors on multiple cell types, possibly mediating distinct phenotypic changes (387).…”

Section: Osteopontinmentioning

confidence: 99%

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

et al. 2020

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Chronic liver disease when accompanied by underlying fibrosis, is characterized by an accumulation of extracellular matrix (ECM) proteins and chronic inflammation. Although traditionally considered as a passive and largely architectural structure, the ECM is now being recognized as a source of potent damage-associated molecular pattern (DAMP)s with immune-active peptides and domains. In parallel, the ECM anchors a range of cytokines, chemokines and growth factors, all of which are capable of modulating immune responses. A growing body of evidence shows that ECM proteins themselves are capable of modulating immunity either directly via ligation with immune cell receptors including integrins and TLRs, or indirectly through release of immunoactive molecules such as cytokines which are stored within the ECM structure. Notably, ECM deposition and remodeling during injury and fibrosis can result in release or formation of ECM-DAMPs within the tissue, which can promote local inflammatory immune response and chemotactic immune cell recruitment and inflammation. It is well described that the ECM and immune response are interlinked and mutually participate in driving fibrosis, although their precise interactions in the context of chronic liver disease are poorly understood. This review aims to describe the known pro-/anti-inflammatory and fibrogenic properties of ECM proteins and DAMPs, with particular reference to the immunomodulatory properties of the ECM in the context of chronic liver disease. Finally, we discuss the importance of developing novel biotechnological platforms based on decellularized ECM-scaffolds, which provide opportunities to directly explore liver ECM-immune cell interactions in greater detail.

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Section: Osteopontinmentioning

confidence: 99%

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

et al. 2020

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“…It is mainly expressed in the olfactory bulb, cerebellum and brainstem neurons, and the expression in the pons and medulla is higher than that in the midbrain. But it is significantly up-regulated in the case of injury or inflammation ( Zhou et al, 2020 ), such as acute brain injury. Activating the P42/44 MAPK and PI3/Akt pathway can lead to the synthesis of a new protein in the cell, and the PI3/Akt pathway plays a key role in cell apoptosis, blood-brain barrier destruction, neurogenesis and angiogenesis.…”

Section: Cross-organ Regulation Of Bone-derived Secreted Proteinmentioning

confidence: 99%

Endocrine Regulation of Extra-skeletal Organs by Bone-derived Secreted Protein and the effect of Mechanical Stimulation

Zhang

Wang

et al. 2021

Front. Cell Dev. Biol.

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Bone serves as the support for body and provide attachment points for the muscles. The musculoskeletal system is the basis for the human body to complete exercise. Studies believe that bone is not only the basis for constructing structures, but also participates in the regulation of organs outside bone. The realization of this function is closely related to the protein secreted by bone. Whether bone can realize their positions in the human body is also related to their secretion. Bone-derived proteins provide a medium for the targeted regulation of bones on organs, making the role of bone in human body more profound and concrete. Mechanical stimulation effects the extra-skeletal organs by causing quantitative changes in bone-derived factors. When bone receives mechanical stimulation, the nichle of bone responds, and the secretion of various factors changes. However, whether the proteins secreted by bone can interfere with disease requires more research. In this review article, we will first introduce the important reasons and significance of the in-depth study on bone-derived secretory proteins, and summarize the locations, structures and functions of these proteins. These functions will not only focus on the bone metabolism process, but also be reflected in the cross-organ regulation. We specifically explain the role of typical bone-derived secretory factors such as osteocalcin (OCN), osteopontin (OPN), sclerostin (SOST) and fibroblast growth factor 23 (FGF23) in different organs and metabolic processes, then establishing the relationship between them and diseases. Finally, we will discuss whether exercise or mechanical stimulation can have a definite effect on bone-derived secretory factors. Understanding their important role in cross-organ regulation is of great significance for the treatment of diseases, especially for the elderly people with more than one basic disease.

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“…It can interact with integrins via Nterminal domains and CD44 receptors via C-terminal domains. OPN interaction with CD44 causes chemotaxis of neutrophils and macrophages, whereas interactions with integrins relay immune cell spreading and activation signals [65][66][67][68][69][70] . OPN (SPP1):Integrin pairings were however not detected in our analysis.…”

Section: Discussionmentioning

confidence: 99%

Circulating osteopontin released by injured kidneys causes pulmonary inflammation and edema

Khamissi¹,

Ning²,

Kefaloyianni³

et al. 2021

Preprint

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Multiorgan failure is devastating, and its mechanisms and mediators are not clear. Tissue injury in one organ appears to trigger disease in remote organs. Kidney and lung are frequently affected, such as when acute kidney injury (AKI) causes acute lung injury (ALI), a frequent clinical condition with high mortality. Here we identify factors secreted from the injured kidney that cause acute lung injury. We developed a murine model mimicking the generation of respiratory failure following acute kidney injury. To identify interorgan crosstalk mediators involved, we performed scRNAseq of mouse kidneys and lungs after AKI. We then applied ligand-receptor (L-R) pairing analysis across cells residing in kidney (ligands) or lung (receptors) to identify kidney-released circulating osteopontin (OPN) as a novel mediator of AKI-induced ALI (AKI-ALI). OPN release very early after AKI largely from tubule cells triggered neutrophil and macrophage infiltration into lungs associated with endothelial leakage, interstitial edema, and functional impairment. Pharmacological or genetic inhibition of OPN prevented AKI-ALI. Transplantation of ischemic wt kidneys into wt mice caused AKI-ALI, while transplantation of ischemic OPN-global-knockout kidneys failed to induce lung endothelial leakage and AKI-ALI, identifying circulating kidney-released OPN as sufficient to cause AKI-ALI in vivo. We show that AKI in humans results in elevations in OPN levels in the serum. Increased serum OPN levels in patients with multiorgan failure have been shown to positively correlate with reduced kidney function, respiratory failure, and mortality. Thus, our results identifying OPN as a mediator of AKI-ALI may have important therapeutic implications in human AKI-ALI and multiorgan failure.

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Osteopontin as a candidate of therapeutic application for the acute brain injury

Cited by 29 publications

References 160 publications

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

Endocrine Regulation of Extra-skeletal Organs by Bone-derived Secreted Protein and the effect of Mechanical Stimulation

Circulating osteopontin released by injured kidneys causes pulmonary inflammation and edema

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