Poster #007, Stanford University
Role of Primary Cilia in Lung Injury and Disease
Mentors: Csenge Rezi, PhD and Peter Jackson, PhD
Idiopathic Pulmonary Fibrosis (IPF) is a progressive disease in which lung scarring impairs gas exchange. Alveolar Type 2 (AT2) cells, the resident alveoli stem cells, repair tissues by dividing and differentiating into AT1 cells after injury. Loss of this regenerative capacity is thought to be central to IPF. During repair, AT2 cells pass through a KRT8+ transitional state before maturing into AT1 cells; these cells persist in fibrotic lungs and contribute to abnormal repair. Primary cilia are small organelles that sense extracellular signals, such as Hedgehog. Defective ciliary signaling after injury promotes fibrosis in other organs. Increased primary cilia has been reported in IPF lungs, yet how ciliation is regulated across the AT2-to-AT1 repair trajectory, remains unknown.
We hypothesize that primary cilia are dynamically regulated on alveolar epithelial cells during injury and repair, that cilium-dependent signaling plays a role in AT2-mediated repair, and that faulty cilia signaling adds to the scarring seen in IPF. To test this, we used immunofluorescence microscopy on mouse lung tissue collected at D0, D7, D12, and D30 after bleomycin injury by a collaborating lab. We quantified primary cilia across KRT8+ transitional cells over the injury-repair time course.
We found at D7 after injury — when repair is most active — both cilia and KRT8+ cells increased and co-localized frequently. Additionally, cilia were visually longer and more prominent on other, neighboring alveolar cells than KRT8+ cells. By D30, both returned to baseline.
Our results suggest that there is an increased number of cilia on KRT8+ transitional cells during active repair, pointing to a possible role for ciliary signaling in alveolar regeneration. Since this is a correlative study, further studies are needed to determine whether ciliary signaling drives repair or whether its dysregulation contributes to fibrosis.