Biglycan: A regulator of hepatorenal inflammation and autophagy

Schulz, Martin; Diehl, Valentina; Trebicka, Jonel; Wygrecka, Małgorzata; Schaefer, Liliana

doi:10.1016/j.matbio.2021.06.001

Cited by 25 publications

(20 citation statements)

References 146 publications

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“…POSTN encodes periostin, a secreted ECM protein, playing a role in wound healing and post-infarction ventricular remodeling ( 41 ). BGN and SPARC participate in ECM organization in various tissues ( 42 , 43 ), and BGN (biglycan) also plays a role in inflammation ( 44 , 45 ). MMP2 and TIMP1 respectively encode matrix metalloproteinase 2 and tissue inhibitor of metalloproteinases 1, necessary for ECM cleaving, especially the collagen fibril ( 46 , 47 ).…”

Section: Discussionmentioning

confidence: 99%

Dominant Myocardial Fibrosis and Complex Immune Microenvironment Jointly Shape the Pathogenesis of Arrhythmogenic Right Ventricular Cardiomyopathy

Dai

et al. 2022

Front. Cardiovasc. Med.

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BackgroundArrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable life-threatening myocardial disease characterized by ventricular arrhythmias and sudden cardiac death. Few studies used RNA-sequencing (RNA-seq) technology to analyze gene expression profiles, hub genes, dominant pathogenic processes, immune microenvironment in ARVC. This study aimed to explore these questions via integrated bioinformatics analysis.MethodsRNA-sequencing datasets of GSE107475, GSE107311, GSE107156, and GSE107125 were obtained from the Gene Expression Omnibus database, including right and left ventricular myocardium from ARVC patients and normal controls. Weighted gene co-expression network analysis identified the ARVC hub modules and genes. Functional enrichment and protein-protein interaction analysis were performed by Metascape and STRING. Single-sample gene-set enrichment analysis (ssGSEA) was applied to assess immune cell infiltration. Transcription regulator (TF) analysis was performed by TRRUST.ResultsThree ARVC hub modules with 25 hub genes were identified. Functional enrichment analysis of the hub genes indicated that myocardial fibrosis was the dominant pathogenic process. Higher myocardial fibrosis activity existed in ARVC than in normal controls. A complex immune microenvironment was discovered that type 2 T helper cell, type 1 T helper cell, regulatory T cell, plasmacytoid dendritic cell, neutrophil, mast cell, central memory CD4 T cell, macrophage, CD56dim natural killer cell, myeloid-derived suppressor cell, memory B cell, natural killer T cell, and activated CD8 T cell were highly infiltrated in ARVC myocardium. The immune-related hub module was enriched in immune processes and inflammatory disease pathways, with hub genes including CD74, HLA-DRA, ITGAM, CTSS, CYBB, and IRF8. A positive linear correlation existed between immune cell infiltration and fibrosis activity in ARVC. NFKB1 and RELA were the shared TFs of ARVC hub genes and immune-related hub module genes, indicating the critical role of NFκB signaling in both mechanisms. Finally, the potential lncRNA–miRNA–mRNA interaction network for ARVC hub genes was constructed.ConclusionMyocardial fibrosis is the dominant pathogenic process in end-stage ARVC patients. A complex immune microenvironment exists in the diseased myocardium of ARVC, in which T cell subsets are the primary category. A tight relationship exists between myocardial fibrosis activity and immune cell infiltration. NFκB signaling pathway possibly contributes to both mechanisms.

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Section: Discussionmentioning

confidence: 99%

Dominant Myocardial Fibrosis and Complex Immune Microenvironment Jointly Shape the Pathogenesis of Arrhythmogenic Right Ventricular Cardiomyopathy

Dai

et al. 2022

Front. Cardiovasc. Med.

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“…Using MatriSomeDB filtering, we found the types of ECM proteins between the ISC and DISC were exactly the same, but the content was different, in that both contained 116 identical matrix proteins ( Figure 6C and https://cdn.amegroups.cn/static/public/atm-22-3969-5.xlsx ), further illustrating decellularization not only removed the inhibitory components of the ISC that are not conducive to regeneration, but also preserved the ECM proteins intact despite their differences in content. Next, we comparatively analyzed the differences in ECM protein contents between ISC and DISC and found DISC had a high abundance of ECM proteins that facilitate axon growth and extension, such as collagens, laminins, Fn1 ( 39 ), and TNC ( 40 ), and low level ECM proteins that inhibit axonal growth and extension including CSPG4 ( 6 , 41 ), Vcan ( 42 ), Acan ( 43 ), Bgn ( 44 ), Clu ( 45 ), Tnr ( 46 ), Dcn ( 47 ), MAG, and Postn ( 48 ). However, in ISC, the expression of these proteins was the opposite of that in DISC, with high expression of axonal growth inhibitory molecules and low expression of promoting molecules ( Figure 6D and https://cdn.amegroups.cn/static/public/atm-22-3969-6.xlsx ), further demonstrating decellularization could remove or decrease the contents arresting axonal growth or regeneration.…”

Section: Discussionmentioning

confidence: 99%

Decellularization alters the unfavorable regenerative adverse microenvironment of the injured spinal cord to support neurite outgrowth

Hu¹,

Shangguan²,

Askar³

et al. 2022

Ann Transl Med

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Background Acellular tissue has been transplanted into the injury site as an external microenvironment to intervene with imbalance microenvironment that occurs after spinal cord injury (SCI) and stimulating axonal regeneration, although the mechanism is unclear. Given decellularization is the key means to obtain acellular tissues, we speculated changes in the internal components of tissue caused by decellularization may be the key reason why acellular tissues affect remodeling of the microenvironment. Methods Complete spinal cord crush in a mouse model was established, and the dynamic of extracellular matrix (ECM) expression and distribution during SCI was studied with immunohistochemistry (IHC). Normal spinal cord (NSC) and 14-day injury spinal cord (ISC) were obtained to prepare the decellularized NSC (DNSC) and decellularized ISC (DISC) through a well-designed decellularization method, and the decellularization effects were evaluated by residual DNA content determination, hematoxylin and eosin staining (H&E), and IHC. Rat dorsal root ganglia (DRG) were co-cultured with NSC, ISC, DNSC, and DISC to evaluate their effect on neurite outgrowth. Furthermore, the mechanisms by which decellularized tissue promotes axonal growth were explored with proteomics analysis of the protein components and function of 14-day ISC and DISC. Results We found the expression of the four main ECM components (collagen type I and IV, fibronectin, and laminin) gradually increased with the progression of SCI compared to NSC, peaking at 14 days of injury then slightly decreasing at 21 days, and the distribution of the four ECM proteins in the ISC also changed dynamically. H&E staining, residual DNA content determination, and IHC showed decellularization removed cellular components and preserved an intact ECM. The results of co-cultured DRG with NSCs, ISCs, DNSCs, and DISCs showed DNSCs and DISCs had a stronger ability in supporting neurite outgrowth than NSC and ISC. We found through proteomics that decellularization could remove proteins associated with inflammatory responses, scarring, and other pathological factors, while completely retaining the ECM proteins. Conclusions Taken together, our findings demonstrate decellularization can optimize the imbalanced microenvironment after SCI by removing components that inhibit spinal cord regeneration, providing a theoretical basis for clinical application of acellular tissue transplantation to repair SCI.

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“…These 3 SLRPs members have some structural similarities and differences, such as different core protein molecular weights (ASPN: 42 kDa; decorin: 36 kDa; biglycan: 38 kDa). [ 19 , 20 ]…”

Section: The Molecular Architecture Of Aspnmentioning

confidence: 99%

Relationship between asporin and extracellular matrix behavior: A literature review

2022

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Asporin (ASPN), as a member of the small leucine-rich repeat proteoglycan family, is a type of protein that is found in the extracellular matrix. Collagen deposition or transformation is involved in a variety of pathological processes. ASPN is identified in cancerous tissue, pathological cardiac tissue, articular cartilage, keloid, and fibrotic lung tissue, and it has a role in the development of cancer, cardiovascular, bone and joint, keloid, and pulmonary fibrosis by interfering with collagen metabolism. This review article summarizes the data on ASPN expressions in mouse and human and highlights that overexpress of ASPN might play a role in a variety of diseases. Although our knowledge of ASPN is currently limited, these instances may help us better understand how it interacts with diseases.

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Biglycan: A regulator of hepatorenal inflammation and autophagy

Cited by 25 publications

References 146 publications

Dominant Myocardial Fibrosis and Complex Immune Microenvironment Jointly Shape the Pathogenesis of Arrhythmogenic Right Ventricular Cardiomyopathy

Dominant Myocardial Fibrosis and Complex Immune Microenvironment Jointly Shape the Pathogenesis of Arrhythmogenic Right Ventricular Cardiomyopathy

Decellularization alters the unfavorable regenerative adverse microenvironment of the injured spinal cord to support neurite outgrowth

Relationship between asporin and extracellular matrix behavior: A literature review

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