Is Osteopontin a Friend or Foe of Cell Apoptosis in Inflammatory Gastrointestinal and Liver Diseases?

Iida, Tomoya; Wagatsuma, Kohei; Hirayama, Daisuke; Nakase, Hiroshi

doi:10.3390/ijms19010007

Cited by 29 publications

(23 citation statements)

References 127 publications

(132 reference statements)

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“…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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“…Notably, the SPP1 gene encodes osteopontin (OPN) whose secreted isoform has been found to be chemotactic to immune cells [ 17 ] and may represent a conserved pro-fibrogenic response to chronic liver injury [ 18 ]. OPN has been implicated in various chronic liver diseases including chronic hepatitis and alcoholic liver disease [ 19 ]. OPN upregulation during liver injury and fibrosis represents a conserved repair-response, and thus OPN levels may provide a useful biomarker for liver fibrosis in NASH in addition to other chronic liver diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, a recent study from Duke University demonstrated that advanced fibrosis (stage 3–4 vs fibrosis stage 0–1) in NAFLD was associated with upregulation of OPN [ 20 ]. In addition to a pro-fibrogenic role for OPN, it also has several pro-inflammatory properties targeting several innate immune cell populations including macrophages, neutrophils and natural killer cells [ 19 ]. A recent study in a murine NASH model demonstrated that antibodies targeting OPN not only attenuated fibrosis but also inflammation, suggesting that targeting OPN in the early stages of NAFLD may be effective in preventing the progression to NASH and fibrosis [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Increased hepatic and circulating chemokine and osteopontin expression occurs early in human NAFLD development

et al. 2020

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Background & aims Non-alcoholic steatohepatitis (NASH), a subtype of non-alcoholic fatty liver disease (NAFLD) that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma, is characterized by hepatic inflammation. Despite evolving therapies aimed to ameliorate inflammation in NASH, the transcriptional changes that lead to inflammation progression in NAFLD remain poorly understood. The aim of this pilot study was to define transcriptional changes in early, non-fibrotic NAFLD using two independent biopsy-proven NAFLD cohorts. Methods We extracted RNA from liver tissue of 40 patients with biopsy-proven NAFLD based on NAFLD Activity Score (NAS) (23 patients with NAS �3, 17 with NAS �5) and 21 healthy controls, and we compared changes in expression of 594 genes involved in innate immune function. Using plasma from an independent cohort of 67 patients with NAFLD and 15 healthy controls, we validated the gene changes observed using a multiplex protein assay. Results Compared to healthy controls, NAFLD patients with NAS �5 had differential expression of 211 genes, while those with NAS �3 had differential expression of only 14 genes. Notably, osteopontin (SPP1) (3.74-fold in NAS �3, 8.28-fold in NAS �5) and CXCL10 (2.27-fold in NAS �3, 8.28-fold in NAS �5) gene expression were significantly upregulated with histologic progression of NAFLD. Plasma osteopontin (SPP1) and CXCL10 are significantly increased in the presence of NAFLD, regardless of histologic grade. In addition, the plasma

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“…Successful replication of a virus relies on the ability to block or delay apoptosis until sufficient progeny have been produced [69]. OPN has been reported to provide the antiapoptotic signal through binding to α v β 3 [70] and CD44 variants v6 and/or v7 [15,[71][72][73]. Thus, it is possible that OPN signaling may help to bypass apoptosis and thereby favor the spread of WNV infection in the CNS.…”

Section: Opn and Wnvmentioning

confidence: 99%

The Roles of Osteopontin in the Pathogenesis of West Nile Encephalitis

Nazneen

Bai

2020

Vaccines

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Osteopontin (OPN), a multifunctional protein encoded by the secreted phosphoprotein-1 (Spp-1) gene in humans, plays important roles in a variety of physiological conditions, such as biomineralization, bone remodeling and immune functions. OPN also has significant roles in the pathogenesis of autoimmune, allergy and inflammatory diseases, as well as bacterial, fungal and viral infections. West Nile virus (WNV), a mosquito-transmitted flavivirus, is the leading agent for viral encephalitis in North America. Recent progress has been made in understanding both the biological functions of OPN and the pathogenesis of WNV. In this review article, we have summarized the current understanding of the biology of OPN and its vital roles in the pathogenesis of WNV encephalitis.

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Is Osteopontin a Friend or Foe of Cell Apoptosis in Inflammatory Gastrointestinal and Liver Diseases?

Cited by 29 publications

References 127 publications

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

Increased hepatic and circulating chemokine and osteopontin expression occurs early in human NAFLD development

The Roles of Osteopontin in the Pathogenesis of West Nile Encephalitis

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