More reasons to quit smoking. Cigarette smoke blocks self-healing processes in lungs

According to a German study, cigarette smoke erodes molecules responsible for renewal of lung cells and certain proteins essential for breathing.

Smoke from cigarettes blocks self-healing processes in the lungs and consequently can lead to chronic obstructive pulmonary disease (COPD), says a new study.

Smoking can lead to chronic obstructive pulmonary disease, which causes cough, bronchitis and breathing difficulties.(Shutterstock)

Researchers at the Helmholtz Zentrum München, partner in the German Centre for Lung Research (DZL), and their international colleagues have reported this finding in the American Journal of Respiratory and Critical Care Medicine.

Cough, bronchitis and breathing difficulties are the typical manifestations of COPD. Exact figures are not available, but estimates assume that 10 to 12% of adults over 40 years of age in Germany suffer from the disease. Experts estimate the national economic costs of the disease at almost six billion euros annually. Scientists around the world are attempting to discover how the disease develops and what biological adjustments can be made to stop it.

One approach involves the lung’s natural self-healing, which no longer takes place in COPD. “In healthy patients, the so-called WNT/beta-catenin signaling pathway is responsible for the lung’s homeostasis. Until now, it was not clear why it was silenced in patients with COPD,” said Dr Melanie Konigshoff, head of the Lung Repair and Regeneration (LRR) Research Unit of the Comprehensive Pneumology Center (CPC) at Helmholtz Zentrum München. She and her team spent the last few years tackling this question in the framework of an ERC Starting Grant and discovered that one of the Frizzled molecules – Frizzled 4 – plays an important role.

“Frizzled 4 is a receptor molecule that sits on the surface of lung cells, where it regulates their self-renewal via WNT/beta-catenin,” said author Wioletta Skronska-Wasek, doctoral candidate at the LRR. “However if the cells are exposed to cigarette smoke, Frizzled 4 disappears from the surface and cell growth comes to a halt.”

The starting point for the current study was the team’s observation that in the lung tissue of COPD patients, and especially that of smokers, there were significantly fewer Frizzled 4 receptors than in non-smokers. “In the next step, we were able to prove in cell culture and model systems that inhibition of Frizzled 4 signalling on the cells led to decreased WNT/beta-catenin activity and consequently to reduced wound healing and repair capacity,” said Dr Ali Önder Yildirim, an expert on the effects of cigarette smoke in the lung. The authors additionally recognized that without the receptor, there was a loss of certain proteins that are important for the structure of lung tissue (including elastin, fibulin and IGF1) and the lung’s elasticity, allowing patients to breathe.

Smoking causes loss of certain proteins essential for the structure of lung tissue and elasticity. (Shutterstock)

To confirm their results, the scientists artificially increased Frizzled 4 levels in a cell culture test to stimulate its production. The increase in Frizzled 4 reactivated the blocked repair process and led to the production of many of the previously reduced proteins.

“The activation of the Frizzled 4 receptor can restore the WNT/beta-catenin signalling pathway and consequently lead to repair in the lung,” said Melanie Konigshoff. This is an exciting starting point for further research which might develop new therapies for COPD patients.

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