2 Molecules Seen as ‘Bona Fide Regulators’ of Lung Scarring and Potential PF Treatments

2 Molecules Seen as ‘Bona Fide Regulators’ of Lung Scarring and Potential PF Treatments

Two molecules secreted by epithelial cells of the lungs — CST3 and GDF15 — “are bona fide regulators” of scarring processes and may point to a new way to treat pulmonary fibrosis, an early study reports.

The study, “Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis,” was published in the journal Cell Death & Disease.

Pulmonary fibrosis is a progressive lung disease associated with a collapse in lung architecture, attributed at least in part to an increase in the growth of cells known as fibroblasts. For lungs to return to a healthy structure after injury, fibroblasts — cells in collective tissue that produces collagen and other wound-healing fibers — must be present, but not at excessive levels.

Epithelial cells line various organs, including the lungs. They are known to secrete small molecules called cytokines, which have been shown to play various roles in regulating fibrosis. But little is known about how cytokines secreted by epithelial cells affect the fibroblast cell population.

Researchers in Seoul, South Korea, conducted a series of experiments to identify cytokines that control fibroblast production to help determine those cytokines that have healing properties and might be developed into therapies.

They grew lung epithelial cells in the lab using media — a liquid with the necessary components for cell growth. But the media  also would come to contain all the cytokines secreted by epithelial cells as they grow. The team then  allowing researchers then introduced lung fibroblasts into the cytokine-rich media to determine those that worked significantly block fibroblasts growth.

Two were seen to inhibit cell growth: cystatin C (CST3) and growth differentiation factor 15 (GDF15). CST3 has previously been shown to block fibrosis, and GDF15 is known to induce cell death.

An analysis of how these two cytokines work found that both molecules inhibit fibroblast growth and activation through a cell signaling pathway known as TGF–Smad.

As expected, when analyzing mouse and human lung tissue undergoing fibrosis, researchers found lower-than-usual CST3 and GDF15 levels. This finding prompted them to investigate the effects of restoring expression of these cytokines in fibrotic lungs.

Using a mouse model of lung fibrosis, they  demonstrated that administering either CST3 or GDF15 led to reduced fibrosis. The two cytokines, given the mice in combination but at half-doses, also were seen to be more effective in preventing fibroblast formation than a single cytokine given at a full dose.

“These results suggest that CST3 and GDF15 are bona fide regulators to prevent excessive proliferation and activation of fibroblasts in injured lungs. These cytokines could be potential therapeutics for ameliorating interstitial lung fibrosis,” the team concluded.


  1. Rose Miller says:

    Will there be a clinical trial on this for IPF patients in the near future? It looks promising.

    Thank you,
    Rose Miller, Allentown, PA

  2. corine quinlan says:

    Just diagnosed I am not willing to give up yet. I live in Dartmouth, NS Canada and not sure if this article is in states however am interested in any other information re fibrosis of the lung. I have had TB as a child – my grandmother and myself went to a sanitorium together. Therefor I have scarring of the lungs but this winter I had 3 antibiotics while also taking metatrexate for Rheumatoid Arthritis. Not sure what doctor allowed this to happen thus I now have fibrois of lungs – help!

  3. Joyce Taylor says:

    I would love to be a canidat of this study, I was diagnosed with IPF 3 years ago, February 2017 I was on the lung transplant list, due to high Antibodies a donor is taking longer than usual..

  4. Ingram Walker Marion says:

    I am a 74 year old living in Scotland. Diagnosed 18 months ago and that was IT!,,. No follow ups , no medication, no clinic visits, have never seen a lung specialist since about five years ago when I developed sarcoidosis
    Don’t know what to do next, doctor will not refer me on, I am insured but even that will not move him

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