4.6 Review

Alveolar Dynamics and Beyond - The Importance of Surfactant Protein C and Cholesterol in Lung Homeostasis and Fibrosis

Journal

FRONTIERS IN PHYSIOLOGY
Volume 11, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2020.00386

Keywords

surfactant protein C; pulmonary fibrosis; alveolar dynamics; lipid metabolism; alveolar macrophages; cholesterol; metaflammation

Categories

Funding

  1. Biomedical Research in Endstage and Obstructive Lung Disease (BREATH)
  2. Member of the German Centre for Lung Research (DZL)
  3. Cluster of Excellence REBIRTH (Regenerative Biology to Reconstructive Therapy Hannover)
  4. HilF program (Hochschulinterne Leistungsforderung, MHH)

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Surfactant protein C (SP-C) is an important player in enhancing the interfacial adsorption of lung surfactant lipid films to the alveolar air-liquid interface. Doing so, surface tension drops down enough to stabilize alveoli and the lung, reducing the work of breathing. In addition, it has been shown that SP-C counteracts the deleterious effect of high amounts of cholesterol in the surfactant lipid films. On its side, cholesterol is a well-known modulator of the biophysical properties of biological membranes and it has been proven that it activates the inflammasome pathways in the lung. Even though the molecular mechanism is not known, there are evidences suggesting that these two molecules may interplay with each other in order to keep the proper function of the lung. This review focuses in the role of SP-C and cholesterol in the development of lung fibrosis and the potential pathways in which impairment of both molecules leads to aberrant lung repair, and therefore impaired alveolar dynamics. From molecular to cellular mechanisms to evidences in animal models and human diseases. The evidences revised here highlight a potential SP-C/cholesterol axis as target for the treatment of lung fibrosis.

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