A factor that causes cancer may actually help prevent pulmonary fibrosis, researchers at China’s Jilin Provincial Cancer Hospital say.
The protein, called TIAM1, is found in higher levels in mouse models of lung fibrosis and human cells exposed to fibrotic stimuli, but experiments showed that it acted to prevent maturation of fibrosis-forming fibroblast cells.
The study, “TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis,” appeared in the journal Experimental and Therapeutic Medicine.
In a first round of experiments, researchers used mice exposed to the fibrosis-triggering chemical bleomycin. They noted higher levels of TIAM1 protein in the fibrotic lung tissue of these animals — a finding they could confirm in human fibroblast cells exposed to the profibrotic factor TGF-beta.
The increase in TIAM1 protein in these cells after exposure to TGF-beta depended on the actions of a pro-inflammatory complex. When this complex was blocked, TGF-beta could no longer trigger a TIAM1 increase.
In this situation, it is impossible for researchers to know if the increase in TIAM1 promoted fibrosis, or if it is a response that restricts the disease process. To find out, the team performed experiments in which they either boosted TIAM1 levels or depleted the protein.
When the protein was present in high concentrations, TGF-beta largely failed to trigger maturation of fibroblasts into fibrosis-promoting cells. And when it was absent, the opposite happened; TGF-beta worked better in promoting fibrosis-producing cells to mature.
In their report, researchers noted that earlier studies show that an absence of TIAM1 makes lab-grown lung cancer cells more invasive. In fact, scientists suspect a link between lung fibrosis and lung cancer, as smokers with idiopathic pulmonary fibrosis are at higher risk of developing lung cancer.
The current study did not report any impact on the invasive properties of the examined cells. Therefore, the team suggested that TIAM1 may serve different roles in fibroblast maturation and cancer cell invasiveness.
Based on the results, the researchers say TIAM1 should be explored as a potential treatment target in pulmonary fibrosis.
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