Circulating thrombospondin 2 levels reflect fibrosis severity and disease activity in HCV-infected patients

Iwadare, Takanobu; Kimura, Takefumi; Tanaka, Naoki; Yamazaki, Tomoo; Wakabayashi, Shun‐ichi; Okumura, Taiki; Kobayashi, Hiroyuki; Yamashita, Yūki; Pydi, Sai Prasad; Nakajima, Tomoyuki; Iwaya, Mai; Sugiura, Ayumi; Joshita, Satoru; Uehara, Takeshi; Umemura, Takeji

doi:10.1038/s41598-022-23357-9

Cited by 7 publications

(16 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, we found that the reductions in serum TSP2 levels only correlated with improvements in liver stiffness, but not with those in HbA1c, BW and hepatic steatosis. Our findings, together with previous studies demonstrating the prognostic significance of baseline circulating TSP2 level in predicting more advanced stages of hepatic fibrosis, 1,8–10 suggested that circulating serum TSP2 level is a potential promising novel hepatic fibrosis biomarker capable of reflecting changes in hepatic fibrosis, and could be further developed as another noninvasive tool for monitoring the severity of hepatic fibrosis.…”

Section: Discussionsupporting

confidence: 74%

“…[5][6][7] Circulating TSP2 was recently identified as a potential novel biomarker of hepatic fibrosis. 1,[8][9][10] In morbidly obese individuals, higher circulating TSP2 levels were associated with increasing severity of hepatic steatosis, inflammation and fibrosis. 1,8 In T2D patients with coexisting NAFLD, baseline circulating TSP2 level was associated with the presence and the development of advanced hepatic fibrosis.…”

Section: Introductionmentioning

confidence: 99%

“…Thrombospondin‐2 (TSP2) is a matricellular protein that modulates several important biological functions including extracellular matrix (ECM) assembly, tissue remodelling, angiogenesis and wound healing 5–7 . Circulating TSP2 was recently identified as a potential novel biomarker of hepatic fibrosis 1,8–10 . In morbidly obese individuals, higher circulating TSP2 levels were associated with increasing severity of hepatic steatosis, inflammation and fibrosis 1,8 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Serum thrombospondin‐2 level changes with liver stiffness improvement in patients with type 2 diabetes

Mak,

Lui,

Fong

et al. 2023

Clinical Endocrinology

View full text Add to dashboard Cite

ObjectiveBaseline circulating thrombospondin‐2 (TSP2) level was identified as a potential novel hepatic fibrosis biomarker that associates with development and progression of hepatic fibrosis in patients with nonalcoholic fatty liver disease and type 2 diabetes. Here, we investigated whether circulating TSP2 levels changed with improvement in liver stiffness (LS), which reflects liver fibrosis on transient elastography.DesignSerum TSP2 levels were measured in participants from a randomized, open‐label intervention study, at baseline and after 24‐weeks treatment of either dapagliflozin 10 mg (N = 30) or sitagliptin 100 mg daily (N = 30). Vibration‐controlled transient elastography was performed to evaluate the severity of hepatic fibrosis and steatosis using LS and controlled attenuation parameter (CAP), respectively.Patients and MeasurementsAmong all 60 participants with similar clinical characteristics at baseline (mean HbA1c 8.9%, CAP 289 dB/m and LS 5.8 kPa), despite similar HbA1c lowering, treatment with dapagliflozin, but not sitagliptin, led to significant improvements in body weight (BW) (p = .012), CAP (p = .015) and LS (p = .011) after 24 weeks.ResultsSerum TSP2 level decreased significantly from baseline in dapagliflozin‐treated participants (p = .035), whereas no significant change was observed with sitagliptin. In correlation analysis, change in serum TSP2 levels only positively correlated with change in LS (r = .487, p = .006), but not with changes in BW, CAP or HbA1c after dapagliflozin treatment.ConclusionsSerum TSP2 level decreased with LS after dapagliflozin treatment, and was independent of improvements in BW, glycemic control and hepatic steatosis, further supporting the potential of serum TSP2 level as a novel hepatic fibrosis biomarker in type 2 diabetes.

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Serum thrombospondin‐2 level changes with liver stiffness improvement in patients with type 2 diabetes

Mak,

Lui,

Fong

et al. 2023

Clinical Endocrinology

View full text Add to dashboard Cite

show abstract

“…Similar ndings were reported from other groups, thus corroborating the ability of TSP2 to estimate disease activity and brosis stage in NAFLD 8 7 . In addition, we earlier reported that serum TSP2 levels re ected brosis severity and disease activity in HCV-infected patients 5 . Based on this accumulating evidence, we hypothesized that a correlation between TSP2 and liver disease activity could also be present in hepatitis B.…”

Section: Discussionmentioning

confidence: 97%

Thrombospondin 2 in Hepatitis B: A Prognostic Insight into Hepatocellular Carcinoma Risk During Nucleos(t)ide Analog Therapy

Okumura,

Kimura,

Ichikawa

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Aims Thrombospondin 2 (TSP2) plays a vital role in collagen/fibrin formation, bone growth, vascular density regulation, hemostasis, and cell adhesion. We earlier revealed close associations of serum TSP2 with histological severity in non-alcoholic fatty liver disease and chronic hepatitis C. The present study investigated the significance of circulating TSP2 in chronic hepatitis B patients. Methods Eighty-seven biopsy-proven chronic hepatitis B patients were analyzed in cross-sectional Study 1 to search for correlations between serum TSP2 levels prior to liver biopsy and clinicopathological parameters. In longitudinal Study 2, 51 chronic hepatitis B patients with long-term follow-up (mean: 7.5 years) were examined for changes in serum TSP2 levels during nucleos(t)ide analog (NA) therapy along with trends in hepatocarciongenesis. Results In Study 1, serum TSP2 levels were not significantly associated with portal inflammation or fibrosis. Study 2 revealed that serum TSP2 was significantly decreased after 48 weeks of NA therapy (P < 0.001). Notably, TSP2 levels at 48 weeks of NA administration (TSP2-48W) were significantly higher in the hepatocellular carcinoma (HCC) (+) group than in the HCC (-) group (P = 0.043). Kaplan-Meier analysis showed that higher TSP2-48W (≥ 24 ng/mL) was associated with future HCC development (P = 0.030). Conclusion Serum TSP2 levels may be a potential predictor of HCC development in hepatitis B patients receiving NA therapy. Longitudinal prospective studies are necessary to validate our findings.

show abstract

“…17,18 Furthermore, a correlation between the degree of fibrosis and inflammation and serum TSP2 levels was observed not only in NAFLD, but also in hepatitis C virus-infected patients. 19,20 Despite these advances, however, the specific liver cell populations responsible for THBS2/TSP2 expression in NAFLD, the underlying mechanisms governing expression dynamics, and the precise role of THBS2/TSP2 in the pathogenesis of NAFLD remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Thrombospondin 2 is a key determinant of fibrogenesis in non‐alcoholic fatty liver disease

Kimura,

Iwadare,

Wakabayashi

et al. 2023

Liver International

Self Cite

View full text Add to dashboard Cite

ObjectiveHepatic overexpression of the thrombospondin 2 gene (THBS2) and elevated levels of circulating thrombospondin 2 (TSP2) have been observed in patients with chronic liver disease. This study aimed to identify the specific cells expressing THBS2/TSP2 in non‐alcoholic fatty liver disease (NAFLD) and investigate the underlying mechanism behind THBS2/TSP2 upregulation.DesignComprehensive NAFLD liver gene datasets, including single‐cell RNA sequencing (scRNA‐seq), in‐house NAFLD liver tissue, and LX‐2 cells derived from human hepatic stellate cells (HSCs), were analysed using a combination of computational biology, genetic, immunological, and pharmacological approaches.ResultsAnalysis of the genetic dataset revealed the presence of 1433 variable genes in patients with advanced fibrosis NAFLD, with THBS2 ranked among the top 2 genes. Quantitative polymerase chain reaction (qPCR) examination of NAFLD livers showed a significant correlation between THBS2 expression and fibrosis stage (r = .349, p < .001). In support of this, scRNA‐seq data and in situ hybridization demonstrated that the THBS2 gene was highly expressed in HSCs of NAFLD patients with advanced fibrosis. Pathway analysis of the gene dataset revealed THBS2 expression to be associated with the transforming growth factor beta (TGFβ) pathway and collagen gene activation. Moreover, the activation of LX‐2 cells with TGFβ increased THBS2/TSP2 and collagen expression independently of the TGFβ‐SMAD2/3 pathway. THBS2 gene knockdown significantly decreased collagen expression in LX‐2 cells.ConclusionsTHBS2/TSP2 is highly expressed in HSCs and plays a role in regulating fibrogenesis in NAFLD patients. THBS2/TSP2 may therefore represent a potential target for anti‐fibrotic therapy in NAFLD.

show abstract

Circulating thrombospondin 2 levels reflect fibrosis severity and disease activity in HCV-infected patients

Cited by 7 publications

References 29 publications

Serum thrombospondin‐2 level changes with liver stiffness improvement in patients with type 2 diabetes

Serum thrombospondin‐2 level changes with liver stiffness improvement in patients with type 2 diabetes

Thrombospondin 2 in Hepatitis B: A Prognostic Insight into Hepatocellular Carcinoma Risk During Nucleos(t)ide Analog Therapy

Thrombospondin 2 is a key determinant of fibrogenesis in non‐alcoholic fatty liver disease

Contact Info

Product

Resources

About