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Enho Mutations Causing Low Adropin: A Possible Pathomechanism of MPO-ANCA Associated Lung Injury

Feng Gao1, Jun Fang2, Falin Chen3

  • 1Department of Pathology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.

Ebiomedicine
|June 23, 2016
PubMed
Abstract

Insights

Mutations in the energy homeostasis gene (Enho) and adropin deficiency are linked to MPO-ANCA lung injury. These factors contribute to pulmonary alveolar hemorrhage and reduced Treg cells in patients and mice.

Area of Science:

  • Genetics and Molecular Biology
  • Immunology
  • Pulmonary Medicine

Background:

  • Myeloperoxidase (MPO) anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis can cause severe lung damage.
  • Limited genetic factors are confirmed in MPO-ANCA lung injury.
  • The role of energy homeostasis gene (Enho) and adropin in this condition is unexplored.

Purpose of the Study:

  • Investigate the role of Enho mutations and adropin deficiency in MPO-ANCA associated lung injury.
  • Determine the genetic variations in Enho in patients with MPO-ANCA vasculitis.
  • Assess the functional impact of adropin deficiency on lung injury.

Main Methods:

  • Analyzed Enho genetic variations in 152 MPO-ANCA patients and 220 healthy controls.
  • Performed functional studies using adropin knockout (AdrKO) mice.
  • Measured serum adropin levels and assessed MPO-ANCA associated lung injury markers in vivo.

Main Results:

  • Identified Enho mutations (p.Ser43Thr, Cys56Trp) in six and five patients, respectively.
  • Found significantly lower serum adropin levels in patients, especially those with Enho mutations (P<0.0001).
  • AdrKO mice exhibited MPO-ANCA associated pulmonary alveolar hemorrhage, reduced eNOS/Akt1 phosphorylation, and loss of Treg cells.

Conclusions:

  • Enho mutations or adropin deficiency are likely molecular triggers for MPO-ANCA associated lung injury.
  • Adropin plays a crucial role in maintaining lung homeostasis in MPO-ANCA vasculitis.
  • Targeting Enho or adropin pathways may offer therapeutic strategies for MPO-ANCA lung injury.
Keywords:
AdropinEnho mutationsMPO-ANCA associated lung injuryeNOS

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