University of California, San Francisco, researchers reported that markers of cellular senescence — a process preventing cells from multiplying uncontrollably — are overly abundant in cells lining lung alveoli in patients with idiopathic pulmonary fibrosis (IPF).
The study, “miR-34 miRNAs Regulate Cellular Senescence in Type II Alveolar Epithelial Cells of Patients with Idiopathic Pulmonary Fibrosis,“ published in the journal PLOS ONE, indicated that microRNAs of the miR-34 family are involved in promoting senescence in these cells, but whether this also contributes to fibrosis still needs to be established.
Cellular senescence works to prevent cells from going into a cancerous state of cell division. Lately, however, researchers have realized that senescence processes are also involved in tissue repair and might trigger inflammation linked to aging.
Analyzing lung tissue from deceased individuals with or without pulmonary fibrosis, the research team specifically focused on type II alveolar epithelial cells — a cell type responsible for secreting a liquid that acts as a surfactant at the air-tissue interface inside the lungs, stopping the lungs from collapsing upon exhalation.
The team started by looking for a protein called SA-βgal, the most common marker of senescent cells in a tissue. The protein was found in a group of cells among fibrosis patients and seemed to be concentrated in areas with fibrosis. In contrast, this protein was completely absent in lung tissue from healthy controls or people with other lung conditions, such as scleroderma or hypersensitivity pneumonitis. Among pulmonary fibrosis patients, researchers also noted three other senescence markers: p16, p21, and p53.
When the team continued looking at isolated type II endothelial cells, they confirmed the observations in the whole lung tissue.
Earlier studies have suggested that microRNAs — a type of RNA molecule involved in controlling gene activity — are able to regulate senescence, so the team analyzed a large set of microRNAs in the cells. It turned out that three factors, miR-34a, miR-34b, and miR-34c, were increased in IPF patients — a finding researchers also confirmed in an additional group of 15 patients and controls.
Researchers then tested if these microRNAs could trigger senescence in cells by boosting their production in cultured cells. As suspected, increasing the microRNA levels also increased the levels of other senescence factors, such as SA-βgal.
“These results show that markers of senescence are uniquely elevated in IPF type II AECs [alveolar epithelial cells] and suggest that the miR-34 family of miRNAs regulate senescence in IPF type II AECs,” they concluded.