Reversal of lung fibrosis in mouse model suggests a novel therapeutic target for pulmonary fibrosis

Science Daily / Cell Death & Differentiation / University of Alabama at Birmingham ^ | August 23, 2021 | Linlin Gu, Ranu Surolia, Jennifer L. Larson-Casey, Chao He, Dana Davis, et al

[ConservativeMind]

Researchers have reversed lung fibrosis in a mouse model of idiopathic pulmonary fibrosis, or IPF.

Mice were given bleomycin for 12 days to establish lung fibrosis, and then treated daily until 21 days with ABT-199, whose medical form is known as Venetoclax. Control bleomycin mice had lung fibrosis with widespread collagen deposition. The bleomycin mice that received ABT-199 had normal lung architecture at 21 days and no collagen deposition.

These results suggest a novel therapeutic target to reverse fibrotic remodeling in the lungs, says study leader A. Brent Carter, M.D.

Pulmonary fibrosis is a chronic disease showing aberrant remodeling of lung tissue. Idiopathic pulmonary fibrosis is the most common form of pulmonary fibrosis and has a high mortality rate within three to five years.

Using lung lavage, they isolated macrophages from people with IPF. They found a marked increase in the macrophage mitochondrial protein Bcl-2 -- a regulator of apoptosis -- as compared to lung macrophages from people without IPF. Mitochondrial Bcl-2 was also elevated in lung macrophages from bleomycin-exposed mice that have lung fibrosis.

…The MCU protein is a channel to bring calcium into the mitochondria, and Cpt1a is an enzyme in mitochondria that is the rate-limiting step for the fatty acid beta-oxidation energy pathway.

The researchers found that Bcl-2 was regulated by MCU, and that silencing MCU caused a significant decrease for Bcl-2 in the mitochondria of lung macrophages.

"Taken together, these observations suggest that fatty acid oxidation provokes apoptosis resistance through the stabilization of Bcl-2 in the mitochondria by binding to Cpt1a," Carter said. "Moreover, these data demonstrate that monocyte-derived macrophages are required for fibrosis progression, and they suggest a novel therapeutic target to prevent progressive aberrant fibrotic remodeling."

[ConservativeMind]

There are dietary BCL-2 inhibitors, which include 1,3 beta glucans, Astragalus, quercetin, taxifolin, EGCG (green and white tea), DIM (Diindolylmethane), sulphur compounds, lycopene, and curcumin.

[The Antiyuppie]

This is fairly amazing.

[TChad]

Good news.

Don't tell Biden, he'll ban Venetoclax.

[Capt. Tom]

Pulmonary fibrosis is a chronic disease showing aberrant remodeling of lung tissue. Idiopathic pulmonary fibrosis is the most common form of pulmonary fibrosis and has a high mortality rate within three to five years. Currently approved medications have limited efficacy.

I was diagnosed with IPF about 5 years ago and had it be reaffirmed by a medical authority on IPF so I could get an experimental drug.

My lungs were perfect and I was a non-smoker and had no reason for my lungs suddenly to look like those of a heavy smoker. That's why Idiopathic is used; it means we don't know why you have it.

Males in my family die from massive heart attacks but IPF looks like it is going to bring me down. But I made it to 86 and that's enough time.

Most men get it in their 60s and they can get lung transplants. I was 80 when diagnosed, and not eligible.

So I am taking the experimental drug "Esbriet", and was able to tolerate it, and I believe it has helped me. -Tom

[ConservativeMind]

I am saddened to hear of your situation. I hope the drug helps.

May we all make it to your age. You are doing much better than most men. Keep it up!

[Trillian]

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