Nerve Growth Factor: A Potential Therapeutic Target for Lung Diseases

Abstract

The lungs play a very important role in the human respiratory system. However, many factors can destroy the structure of the lung, causing several lung diseases and, often, serious damage to people's health. Nerve growth factor (NGF) is a polypeptide which is widely expressed in lung tissues. Under different microenvironments, NGF participates in the occurrence and development of lung diseases by changing protein expression levels and mediating cell function. In this review, we summarize the functions of NGF as well as some potential underlying mechanisms in pulmonary fibrosis (PF), coronavirus disease 2019 (COVID-19), pulmonary hypertension (PH), asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Furthermore, we highlight that anti-NGF may be used in future therapeutic strategies.

Keywords: coronavirus disease 2019; lung; nerve growth factor; pathway.

Figure 1

NGF exerts its function by activating TrkA and p75NTR. Activation of TrkA induces differentiation, proliferation, and survival of the target cell, while p75NTR activation induces apoptosis.

Figure 2

The influence of NGF on lung disease. NGF is expressed in many cells in the lung. Once released, NGF could stimulate diverse types of cells involved in many processes in lung diseases. The relationships between NGF and respective lung diseases are described in the following sections. The blue arrows represent the relationship between NGF and PF; the blue dotted arrow represents a potential effect; the gray arrows represent the relationship between NGF and PH; the green arrows indicate the relationship between NGF and asthma; the purple arrows represent the relationship between NGF and COPD; and the red arrows represent the relationship between NGF and lung cancer.

Figure 3

The signaling pathways related to NGF in lung diseases. NGF upregulates these factors to cause the development of lung diseases. Anti-NGF, which regulates the RhoA–ROCK, TGF-β1–SMAD3, and NGF–TrkA pathways, can improve those lung diseases. The black line indicates the pathway affecting PF; the gray lines indicate pathways affecting PH; the green lines indicate pathways affecting asthma; the orange lines indicate pathways affecting lung cancer; and the yellow lines indicate pathways affecting COPD.