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Review
. 2024 Sep 23;5(10):e744.
doi: 10.1002/mco2.744. eCollection 2024 Oct.

Pulmonary fibrosis: pathogenesis and therapeutic strategies

Jianhai Wang  1   2   3   4 , Kuan Li  1   2   4 , De Hao  1 , Xue Li  1   2   4 , Yu Zhu  5   6 , Hongzhi Yu  4 , Huaiyong Chen  1   2   3   4
Affiliations
Review

Pulmonary fibrosis: pathogenesis and therapeutic strategies

Jianhai Wang et al. MedComm (2020). .

Abstract

Pulmonary fibrosis (PF) is a chronic and progressive lung disease characterized by extensive alterations of cellular fate and function and excessive accumulation of extracellular matrix, leading to lung tissue scarring and impaired respiratory function. Although our understanding of its pathogenesis has increased, effective treatments remain scarce, and fibrotic progression is a major cause of mortality. Recent research has identified various etiological factors, including genetic predispositions, environmental exposures, and lifestyle factors, which contribute to the onset and progression of PF. Nonetheless, the precise mechanisms by which these factors interact to drive fibrosis are not yet fully elucidated. This review thoroughly examines the diverse etiological factors, cellular and molecular mechanisms, and key signaling pathways involved in PF, such as TGF-β, WNT/β-catenin, and PI3K/Akt/mTOR. It also discusses current therapeutic strategies, including antifibrotic agents like pirfenidone and nintedanib, and explores emerging treatments targeting fibrosis and cellular senescence. Emphasizing the need for omni-target approaches to overcome the limitations of current therapies, this review integrates recent findings to enhance our understanding of PF and contribute to the development of more effective prevention and management strategies, ultimately improving patient outcomes.

Keywords: biomarkers; endothelium; epithelium; immune cells; microbiome.

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Conflict of interest statement

The authors declare no conflict of financial interest.

Figures

FIGURE 1
FIGURE 1
PF risk factors. This diagram illustrates the multifactorial risk factors associated with PF, categorized into four main groups: demographic/clinical, occupational and environmental exposures, genetic factors, and lifestyle factors. This figure was designed using BioRender (https://biorender.com/).
FIGURE 2
FIGURE 2
Cellular and microbiome contributions to PF. This schematic illustrates the various cell types and microbiome components involved in the pathogenesis of PF, highlighting their roles and interactions within the lung microenvironment. This figure was designed using BioRender (https://biorender.com/).
FIGURE 3
FIGURE 3
A panoramic understanding of PF toward comprehensive multitargeted interventions. This figure illustrates the interconnected and mutually reinforcing relationship between the study of mechanisms, diagnosis, and treatment of PF. The cycle begins with understanding the mechanisms underlying PF, which leads to the formulation of novel hypotheses. These hypotheses drive the development of new diagnostic tools and classification efforts, enhancing the ability to identify and treat the disease accurately. The insights gained from diagnostics inform therapeutic strategies, leading to novel interventions that improve patient outcomes. As new therapies are implemented, they provide feedback that refines our understanding of the mechanisms and diagnostics, thus continuing the cycle of innovation and improvement. Throughout this process, various omics technologies are utilized to explore and elucidate the complexities of PF, ensuring a comprehensive and detailed approach to its study and management. This figure was designed using BioRender (https://biorender.com/).
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