CCN1 expression in hepatocytes contributes to macrophage infiltration in nonalcoholic fatty liver disease in mice

Bian, Zhaolian; Peng, Yanshen; You, Zhengrui; Wang, Qixia; Miao, Qi; Liu, Yuan; Han, Xiaofeng; Qiu, Dekai; Li, Zhiping; Ma, Xiong

doi:10.1194/jlr.m026013

Cited by 54 publications

(57 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pro-inflammatory role of CCN1 has been confirmed in independent experimental studies, demonstrating its ability to induce cytokine secretion [21,32] and to affect chemotaxis [19,20,36]. As an immediate-early gene, CCN1 is activated within minutes of cellular stimulation without requiring de novo protein synthesis [38], which may suggest that it is able to act as an upstream mediator of cytokine activation.…”

Section: Discussionmentioning

confidence: 63%

“…Attempting to identify the potential mechanisms behind these regulations, we demonstrated that CCN1 expression in parenchymal cells is sensitive to cytokine exposure in vitro. However, accumulating evidence now suggests that CCN1 may also possess pro-inflammatory capabilities [19][20][21], indicating that this immediate early gene may be involved in the initial promotion of the inflammatory response. The present study was undertaken to investigate whether CCN1 is activated at local sites of acute tissue injury in humans and to assess its temporal relationship with the activation of the inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Postoperative Accumulation of Cyr61/CCN1 in Surgical Wound Fluid Precedes Cytokine Activation and is Disparate from Systemic Alterations

Hviid¹,

Pripp²,

Aasen³

et al. 2014

J Infect Dis Ther

View full text Add to dashboard Cite

Background: Cysteine-rich protein 61 (Cyr61/CCN1) is a multifunctional matricellular protein that has recently emerged as a potential player in injury-repair mechanisms involving the regulation of inflammatory responses. Experimental research has revealed the pro-inflammatory effects and chemotactic capacities of this protein, and clinical investigations have found it to be elevated in patients with chronic inflammatory conditions. However, its regulation at sites of acute tissue injury and inflammation in humans has not been investigated.

show abstract

Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Postoperative Accumulation of Cyr61/CCN1 in Surgical Wound Fluid Precedes Cytokine Activation and is Disparate from Systemic Alterations

Hviid¹,

Pripp²,

Aasen³

et al. 2014

J Infect Dis Ther

View full text Add to dashboard Cite

show abstract

“…There are several attributes of CYR61/CCN1 that may critically impact the different steps in fibrosis progression or resolution. One study for example has shown that the expression of this matricellular protein in hepatocytes contributes to the content of macrophage infiltration in models of NAFLD in mice through the TLR4/myeloid differentiation primary response gene 88 (MyD88)/AP-1 pathway [69] . On the other hand, it was demonstrated that CYR61/ CCN1 is a critical promoter of fibrosis resolution by triggering cellular senescence in activated HSC and portal MFBs through integrin-dependent mechanisms [41] .…”

Section: Targeting Matrix Formation or Remodelingmentioning

confidence: 99%

Liver Fibrosis: From Pathogenesis to Novel Therapies

Weiskirchen

Tacke²

2016

Dig Dis

130

100

View full text Add to dashboard Cite

Chronic liver injury is accompanied by a dysbalanced scarring process, termed fibrosis. This process is mainly driven by chronic inflammation and an altered activity of a multitude of different chemokines and cytokines, resulting in the infiltration by immune cells (especially macrophages) and increase of matrix-expressing cell types. These processes might lead to cirrhosis representing the end-stage of fibrosis. Recent clinical studies comprising patients successfully treated for viral hepatitis showed that liver fibrogenesis and even cirrhosis may be reverted. The hepatic capacity to remodel scar tissue and to revert into a normal liver follows specific mechanistic principles that include the termination of chronic tissue damage, shifting the cellular bias from inflammation to resolution, initiation of myofibroblast apoptosis or senescence and, finally, fibrinolysis of excess scar tissue. The plurality of molecular and cellular triggers involved in initiation, progression and resolution of hepatic fibrogenesis offers an infinite number of therapeutic possibilities. For instance, inflammatory macrophages can be targeted via inhibition of chemokine CCL2 or its receptor CCR2 (e.g., by cenicriviroc) as well as by transfer of restorative macrophage subsets. Another target is galectin-3 that acts at various stages along the continuum from acute to chronic inflammation. Profibrogenic cytokines (e.g., transforming growth factor-β), matricellular proteins (e.g., CCN1/CYR61) or signaling pathways involved in fibrogenesis offer further possible targets. Other options are the application of therapeutic antibodies directed against components involved in biogenesis or remodeling of connective tissue such as lysyl oxidase-like-2 or synthetic bile acids like obeticholic acid that activate the farnesoid X receptor and was antifibrotic in a phase 2 study (FLINT trial). Factors affecting the gut barrier function or the intestinal microbiome further expanded the repertoire of drug targets. In this review, we discuss novel concepts in resolution of hepatic fibrosis and focus on drug targets that might be suitable to trigger resolution of fibrosis.

show abstract

“…Resident hepatic macrophages become activated during NASH and contribute to disease progression 60 ; however, infiltration of new macrophages to the liver also occurs and contributes to NASH-induced pathology. 61,62 Future studies will be needed to evaluate the role of resident versus recruited macrophages in post-SCI hepatic pathology after SCI.…”

Section: Sauerbeck Et Almentioning

confidence: 99%

Spinal Cord Injury Causes Chronic Liver Pathology in Rats

Sauerbeck

Laws

Bandaru

et al. 2015

Journal of Neurotrauma

View full text Add to dashboard Cite

Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model. Histologic evidence showed excess lipid accumulation in the liver for at least 21 days post-injury after cervical or midthoracic SCI. Lipidomic analysis revealed an acute increase in hepatic ceramides as well as chronically elevated lactosylceramide. Post-SCI hepatic changes also included increased proinflammatory gene expression, including interleukin (IL)-1a, IL-1b, chemokine ligand-2, and tumor necrosis factor-a mRNA. These were coincident with increased CD68 + macrophages in the liver through 21 days post-injury. Serum alanine transaminase, used clinically to detect liver damage, was significantly increased at 21 days post-injury, suggesting that early metabolic and inflammatory damage preceded overt liver pathology. Surprisingly, liver inflammation was even detected after lumbar SCI. Collectively, these results suggest that SCI produces chronic liver injury with symptoms strikingly similar to those of nonalcoholic steatohepatitis (fatty liver disease). These clinically significant hepatic changes after SCI are known to contribute to systemic inflammation, cardiovascular disease, and metabolic syndrome, all of which are more prevalent in persons with SCI. Targeting acute and prolonged hepatic pathology may improve recovery and reduce long-term complications after SCI.

show abstract

CCN1 expression in hepatocytes contributes to macrophage infiltration in nonalcoholic fatty liver disease in mice

Cited by 54 publications

References 32 publications

Postoperative Accumulation of Cyr61/CCN1 in Surgical Wound Fluid Precedes Cytokine Activation and is Disparate from Systemic Alterations

Postoperative Accumulation of Cyr61/CCN1 in Surgical Wound Fluid Precedes Cytokine Activation and is Disparate from Systemic Alterations

Liver Fibrosis: From Pathogenesis to Novel Therapies

Spinal Cord Injury Causes Chronic Liver Pathology in Rats

Contact Info

Product

Resources

About