Regeneration-Associated Transitional State Cells in Pulmonary Fibrosis

• Published in: International journal of molecular sciences Vol. 23; no. 12; p. 6757
• Main Authors: Shen, Mengxia, Luo, Ziqiang, Zhou, Yan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.06.2022; MDPI
• Subjects: Alveolar Epithelial Cells - metabolism; alveolar regeneration; Alveoli; Cell cycle; Cell Differentiation - physiology; Disease; Epithelium; Extracellular matrix; Fibrosis; Humans; Lung - pathology; Lung diseases; Lung Injury - pathology; Lungs; Parenchyma; Pathogenesis; Pulmonary fibrosis; Pulmonary Fibrosis - metabolism; Repair; Review; Senescence; Severe acute respiratory syndrome coronavirus 2; Therapeutic targets; transitional state cell; alveolar regeneration; transitional state cell; pulmonary fibrosis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23126757

Pulmonary fibrosis is a chronic, progressive fibrosing interstitial disease. It is characterized by fibroblast proliferation, myofibroblast activation, and massive extracellular matrix deposition. These processes result in loss of lung parenchyma function. The transdifferentiation of alveolar epithelial type II (AEC2) to alveolar epithelial type I cells (AEC1) plays an important role in the epithelial repair after lung injury. Pulmonary fibrosis begins when this transdifferentiation process is blocked. Several recent studies have found that novel transitional state cells (intermediate states in the transdifferentiation of AEC2 to AEC1) can potentially regenerate the alveolar epithelium surface and promote a repair process. During the AEC2 to AEC1 trans-differentiation process after injury, AEC2 lose their specific markers and become transitional state cells. Furthermore, transdifferentiation of transitional state cells into AEC1 is the critical step for lung repair. However, transitional cells stagnate in the intermediate states in which failure of transdifferentiation to AEC1 may induce an inadequate repair process and pulmonary fibrosis. In this review, we focus on the traits, origins, functions, and activation of signaling pathways of the transitional state cell and its communication with other cells. We also provide a new opinion on pulmonary fibrosis pathogenesis mechanisms and novel therapeutic targets.