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Table 1 The possible involvement of MK overexpression to SARS-CoV-2 manifestations

From: The growth factor/cytokine midkine may participate in cytokine storm and contribute to the pathogenesis of severe acute respiratory syndrome coronavirus 2-infected patients

Manifestations of SARS-CoV-2 Pathophysiological cell functions of midkine Reference
Pulmonary inflammation • Recruitment of inflammatory cells
• Cytokine release from neutrophils and macrophages
• Enhancement of fibrinolytic activity
Takada 1997 [11]
Wang 2008 [41]
Zhang 2015 [47]
Misa 2017 [48]
Pulmonary hypoxia • Inducing hypoxia via inflammation
• Binding of HIF1-α to hypoxia-responsive elements located in the MK promoter
Eltzschig 2011 [21]
Minamino 2001 [23]
Cramer 2003 [25]
Walmsley 2005 [26]
Pulmonary fibrosis, ARDS • Regulating inflammatory cell migration into the lung and induction of TNF-α and TGF-β expression
• MK–RAS pathway
Zhang 2015 [47]
Misa 2017 [48]
You 2008 [44]
Hobo 2009 [12]
Pulmonary RAS dysregulation • Increasing pathophysiological actions of Ang II via expression of ACE Hobo 2009 [12]