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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]