The growth factor midkine may play a pathophysiological role in rheumatoid arthritis

Emiko, Shindo; Nanki, Toshihiro; Kusunoki, Natsuko; Shikano, Kotaro; Kawazoe, Mai; Sato, Hiroshi; Kaneko, Kaichi; Muraoka, Sei; Kaburaki, Makoto; Akasaka, Yoshikiyo; Shimada, Hideaki; Hasunuma, Tomoko; Kawai, Shinichi

doi:10.1080/14397595.2016.1179860

Cited by 36 publications

(44 citation statements)

References 33 publications

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“…Therefore, these findings suggest that serum Midkine level could be a useful marker for RA disease activity. However, contradictory to our results, the RF high titer was found to be correlated with the serum Midkine in several studies that suggest its relation with the poor prognosis of RA 18 21 26…”

Section: Discussioncontrasting

confidence: 99%

“…Accordingly, we suggest that serum Midkine may be useful in the diagnosis of RA and to detect the disease activity. In agreement with our results, a study conducted by Shindo et al ,21 detected a high level of serum Midkine in patients with RA and the overexpression of Midkine protein and mRNA in RA synovial tissues as well as the cultured rheumatoid synovial fibroblasts (RSFs). Previous functional studies detected that Midkine is significantly upregulated in inflamed synovial tissue during an active RA flare in contrast to synovial tissue of healthy patients 16.…”

Section: Discussionsupporting

confidence: 93%

“…Growing evidences suggested that Midkine contributed to the inflammation process of the synovial tissues of patients with RA via promoting the inflammatory cells accumulation in synovial tissue and synovial fluid either directly through stimulating the neutrophil migration16 or indirectly via enhancing the production of interleukin-6 (IL-6), IL-8, and chemokine (C-C motif) ligand 2 (CCL2) by RSFs. IL-6 was found to regulate immune cell activation 21. IL-8 induces angiogenesis and also exhibits a chemoattractant activity for neutrophils and dendritic cell 27.…”

Section: Discussionmentioning

confidence: 99%

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Diagnostic Value of the Serum Midkine in Patients with Rheumatoid Arthritis

Ghafar

Haleem

Shahba

et al. 2020

Journal of Investigative Medicine

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Early diagnosis and detection of rheumatoid arthritis (RA) activity which is a potential therapeutic target, depends mainly on clinical presentation. However, laboratory tests may contribute to diagnosis and disease activity assessment of RA. This study aims to evaluate the accuracy of serum Midkine as serological marker for RA diagnosis and its activity detection. All patients with RA were recruited during the period from January 2016 to August 2018 in addition to healthy subjects as control. Serum Midkine level was estimated using enzyme immunoassay. The accuracy was determined for serum Midkine against the used American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for RA diagnosis and disease activity score derivative for 28 joints-erythrocyte sedimentation rate (ESR) score for assessment of RA disease activity. A total of 211 of patients with RA (group I) were enrolled in this study with 112 healthy subjects (group II). Patients with RA were divided into two subgroups according to the disease activity; patients with active RA (group IA) and RA in remission (group IB). We detected that the area under curve (AUC) of serum Midkine level (AUC=0.851) was significantly lower than that of rheumatoid factor IgM and anti-cyclic citrullinated peptide IgG for RA diagnosis. However, Midkine presents a significantly higher diagnostic accuracy (AUC=0.939) in detecting RA activity than that offered by C reactive protein (CRP) or ESR. Our study suggested that serum Midkine is a potential serological marker for detection of active inflammatory state with higher diagnostic accuracy than other inflammatory markers as CRP or ESR. Therefore, it can be used as an inflammatory marker for detection of disease activity rather than diagnosis of RA.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Diagnostic Value of the Serum Midkine in Patients with Rheumatoid Arthritis

Ghafar

Haleem

Shahba

et al. 2020

Journal of Investigative Medicine

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“…Plasma MK was elevated in patients with systemic lupus erythematosus which was correlated with IL-17 (11). In rheumatoid arthritis (RA) patients, high MK levels were found to implicated in the pathogenesis of RA and was associated with IL-6 and IL-8 (12,13). In acute and chronic kidney injuries like ischemia/reperfusion injury and diabetic nephropathy, the expression of MK was upregulated and promotes migration of neutrophils and macrophages, hence MK deficiency may show less renal damage (14,15).…”

Section: Discussionmentioning

confidence: 99%

The Effects of 3,4-methylenedioxy- methamphetamine on Neurogenesis in the Hippocampus of Male Rats

Asl

Moravej

Kowsari

et al. 2020

Basic Clin. Neurosci. J.

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Introduction: Midkine (MK), a heparin-binding growth factor, is involved in neurological diseases by mediating the inflammatory responses through enhancing the leukocyte migration. The present study assesses the serum concentration of this growth factor among newly multiple sclerosis (MS) and neuromyelitis optica (NMO). Methods: The present research, as a cross-sectional study, which performed at Isfahan University of Medical Sciences. All samples were selected from patients who visited Kashani and Alzahra hospital during two years 2014-2016. The MK level was assessed in 80 new cases of MS, 80 NMO patients and 80 healthy subjects. After collecting blood sera samples, MK serum level was measured using the ELISA. Data were analyzed by SPSS statistical software. Results: The mean of MK level was 1038.58 ± 44.73 pg/ml in MS group, which was significantly higher compared with the mean of MK level in NMO (872.62 ± 55.42 pg/ml) and control groups (605.02 ± 9.42 pg/ml). Conclusion: Overall, these results demonstrated MK plays a prominent role in inflammatory reactions and also in neuroautoimmune diseases, especially in MS. So, the MK level may be applied to earlier diagnosis and also prevention of disease progression by using a special inhibitor.

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“…Midkine has been proved to be elevated both in plasma and tissues during sepsis [11,12], however, its effects on the organ function was under debate, midkine seemed to have an organ-dependent effect, which showed a protective effect in acute cardiac infarction [28], with angiogenesis promotion [29] and vascular endothelial repairment [30], but a deleterious effect in kidney [31], lung injury [32,33] and autoimmune diseases [34]. In the present study, we found high circulating midkine was correlated to the severity lung injury induced by sepsis.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Midkine Inhibition Ameliorates Sepsis Induced Lung Injury via ACE/Ang II Pathway

Xu¹,

Chang²,

Sun³

et al. 2020

Preprint

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BackgroundMidkine is a multi-functional molecule participating in a various key pathological process. We aimed to evaluate the change of midkine in sepsis and its association with pulmonary function, as well as the mechanism by which midkine induced lung injury in sepsis. MethodsThe peripheral blood sample of septic patients on admission was obtained and measured for midkine, angiotensin-converting enzyme and angiotensin II. Cecal ligation and puncture (CLP) mouse model was used, and adeno-associated virus (AAV) was stilled trans-trachea for regional targeting midkine expression. The lung injury was evaluated, comparing the severity of lung injury. Furthermore, we studied the in vitro mechanism of midkine activates ACE system by using inhibitors targeting candidate receptors of midkine, and its effects on the vascular endothelial cells.ResultsPlasma midkine was significantly elevated in sepsis, and was closely associated with ACE system. Both circulating and lung midkine was increased in CLP mouse, and was related to severe lung injury. Regional interfering midkine expression in lung tissue by AAV could alleviate acute lung injury in CLP model. In vitro study elucidated that Notch 2 participated in the activation of ACE system and angiotensin II release, induced by midkine and triggered vascular endothelial injury by angiotensin II induced ROS production.ConclusionsMidkine participated in the process of sepsis induced lung injury, which was due to the activation of ACE system and angiotensin II release, triggering ROS production.Trial registration Clinicaltrials.gov NCT02605681. Registered 12 November 2015.

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The growth factor midkine may play a pathophysiological role in rheumatoid arthritis

Abstract: The serum MK level could be a marker of disease activity in RA and an indicator of a poor prognosis. MK may have a role in the pathogenesis of RA via induction of inflammatory mediators.

Cited by 36 publications

References 33 publications

Diagnostic Value of the Serum Midkine in Patients with Rheumatoid Arthritis

Diagnostic Value of the Serum Midkine in Patients with Rheumatoid Arthritis

The Effects of 3,4-methylenedioxy- methamphetamine on Neurogenesis in the Hippocampus of Male Rats

Pulmonary Midkine Inhibition Ameliorates Sepsis Induced Lung Injury via ACE/Ang II Pathway

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The growth factor midkine may play a pathophysiological role in rheumatoid arthritis

Abstract: The serum MK level could be a marker of disease activity in RA and an indicator of a poor prognosis. MK may have a role in the pathogenesis of RA via induction of inflammatory mediators.

Cited by 36 publications

References 33 publications

Diagnostic Value of the Serum Midkine in Patients with Rheumatoid Arthritis

Diagnostic Value of the Serum Midkine in Patients with Rheumatoid Arthritis

The Effects of 3,4-methylenedioxy- methamphetamine on Neurogenesis in the Hippocampus of Male Rats

Pulmonary Midkine Inhibition Ameliorates Sepsis Induced Lung Injury via ACE/Ang II&nbsp;Pathway

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Pulmonary Midkine Inhibition Ameliorates Sepsis Induced Lung Injury via ACE/Ang II Pathway