A Clinical Diagnostic Study: Fibulin-2 is a Novel Promising Biomarker for Predicting Infection

Li, Shidan; Jiang, Hao; Xing, Wei; Wang, Shao-Chuan; Zhang, Yao; Li, Youbin; Mao, Constance; Zeng, Delian; Lan, Ping; Tang, Dongqin; Zhan, Jijie; Li, Lei; Xu, Xiang; Fei, Jun

doi:10.1007/s40121-022-00622-y

Cited by 4 publications

(5 citation statements)

References 47 publications

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“…As reported in previous studies, fibulin‐2 is closely related to posttraumatic skin healing and is involved in the tumor immune process 22,23 . Additionally, in our previous study, we found that fibulin‐2 expression was increased in the plasma of infected patients, demonstrating that fibulin‐2 is associated with infection 6 . Based on the above reasons, we speculate that fibulin‐2 may be associated with posttraumatic immune dysfunction.…”

Section: Introductionsupporting

confidence: 77%

“…22,23 Additionally, in our previous study, we found that fibulin-2 expression was increased in the plasma of infected patients, demonstrating that fibulin-2 is associated with infection. 6 Based on the above reasons, we speculate that fibulin-2 may be associated with posttraumatic immune dysfunction. To explore the relationship between fibulin-2 and bone trauma and posttraumatic immune dysfunction, we collected blood samples from patients with bone trauma (bone trauma group), patients who recovered from bone trauma during the same time period (recovered from bone trauma group) and volunteers without bone trauma.…”

Section: Introductionmentioning

confidence: 88%

“…As a result, some patients die in the prehospital emergency phase. 6,7 Even though some patients survive the emergency phase, they still need to overcome traumatic stress, including disorders of the internal environment and immune dysfunction. More seriously, some patients are prone to secondary infections due to immune dysfunction after bone trauma.…”

Section: Introductionmentioning

confidence: 99%

“…Patients with bone trauma often experience hemorrhagic shock due to severe bleeding. As a result, some patients die in the prehospital emergency phase 6,7 . Even though some patients survive the emergency phase, they still need to overcome traumatic stress, including disorders of the internal environment and immune dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Fibulin‐2: A potential regulator of immune dysfunction after bone trauma

Jiang

Wang

et al. 2023

Immunity Inflam & Disease

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Objectives To reveal the relationship between the fibulin‐2 protein and immune dysfunction after bone trauma. Methods Individuals who were admitted to the study were divided into a bone trauma group, a recovered from bone trauma group and a volunteer without bone trauma group based on the reason for admission. Fibulin‐2 levels in the three groups were compared. Fibulin‐2‐knockout (fibulin‐2−/−) mice and wild‐type (WT) mice were used to detect susceptibility to infection. Hematoxylin and eosin (HE) staining and immunohistochemical staining were employed to observe pathological changes in each organ from fibulin‐2−/− mice and WT mice. Results In total, 132 patients were enrolled in this study. The fibulin‐2 level in the bone trauma group was lower than that in the recovered bone trauma group (3.39 ± 1.41 vs. 4.30 ± 1.38 ng/mL, t = 2.948, p < .05) and also lower than that in the volunteers without bone trauma group (3.39 ± 1.41 vs. 4.73 ± 1.67 ng/mL, t = 4.135, p < .05). Fibulin‐2−/− mice are more prone to infection. Compared with those in WT mice, spleen function and thymus function in fibulin‐2−/− mice were impaired. Immunohistochemical staining revealed that compared with those in WT mice, significantly fewer CD4+ T cells, CD8+ T cells, and CD19+ B cells were noted in the spleen and thymus of fibulin‐2−/− mice. Conclusions The plasma fibulin‐2 level was lower in patients with bone trauma. Decreased fibulin‐2 is associated with immune dysfunction after bone trauma.

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Section: Introductionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fibulin‐2: A potential regulator of immune dysfunction after bone trauma

Jiang

Wang

et al. 2023

Immunity Inflam & Disease

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“…In our previous study, we found that Fibulin2 protein expression was upregulated in the plasma after infection 21 . Furthermore, proteomic analysis revealed that Fibulin2 expression was elevated in infected bone.…”

Section: Introductionmentioning

confidence: 88%

Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing

Xing

Wang

et al. 2023

Exp Mol Med

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Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

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Osteoporosis: Emerging targets on the classical signaling pathways of bone formation

Li,

Xue,

2024

European Journal of Pharmacology

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A Clinical Diagnostic Study: Fibulin-2 is a Novel Promising Biomarker for Predicting Infection

Cited by 4 publications

References 47 publications

Fibulin‐2: A potential regulator of immune dysfunction after bone trauma

Fibulin‐2: A potential regulator of immune dysfunction after bone trauma

Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing

Osteoporosis: Emerging targets on the classical signaling pathways of bone formation

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