Scgb3a2, a member of the secretoglobin superfamily, is a small cytokine-like secretory protein predominantly expressed in airway epithelial cells, especially club cells in the lungs and trachea [3]. It has anti-inflammatory, antifibrotic, growth factor, and anti-cancer activities [3]. The protein may influence various lung-related biological processes through different pathways, such as those related to apoptosis, inflammation, and cell differentiation [1,2,3]. Genetic models like knockout mice are valuable for studying its functions.

In Scgb3a2-null mice, an exacerbated ovalbumin-induced allergic pulmonary inflammation was observed in congenic mice, indicating its anti-inflammatory property [2]. In another study, Scgb3a2-null mice showed exacerbated house dust mite-induced allergic airway inflammation, suggesting that Scgb3a2 may modulate the CCR4-CCL17 pathway to exert anti-inflammatory effects [4]. Also, in acrolein-induced apoptosis in mouse fibroblast cells, Scgb3a2 inhibited apoptosis through decreased p53 phosphorylation, not by altering ROS levels [1].

In conclusion, Scgb3a2 plays essential roles in anti-inflammation, anti-apoptosis and potentially other biological processes in the context of lung-related diseases. The gene knockout mouse models have been crucial in revealing its role in allergic airway inflammation and acrolein-induced apoptosis, providing insights into its potential as a therapeutic target for chronic obstructive pulmonary disease and allergic airway diseases [1,2,4].

References:

1. Kurotani, Reiko, Shima, Reika, Miyano, Yuki, Abe, Hiroyuki, Kimura, Shioko. 2015. SCGB3A2 Inhibits Acrolein-Induced Apoptosis through Decreased p53 Phosphorylation. In Acta histochemica et cytochemica, 48, 61-8. doi:10.1267/ahc.14065. https://pubmed.ncbi.nlm.nih.gov/26019375/

2. Kido, Taketomo, Yoneda, Mitsuhiro, Cai, Yan, Ward, Jerrold M, Kimura, Shioko. 2014. Secretoglobin superfamily protein SCGB3A2 deficiency potentiates ovalbumin-induced allergic pulmonary inflammation. In Mediators of inflammation, 2014, 216465. doi:10.1155/2014/216465. https://pubmed.ncbi.nlm.nih.gov/25242865/

3. Kimura, Shioko, Yokoyama, Shigetoshi, Pilon, Aprile L, Kurotani, Reiko. 2022. Emerging role of an immunomodulatory protein secretoglobin 3A2 in human diseases. In Pharmacology & therapeutics, 236, 108112. doi:10.1016/j.pharmthera.2022.108112. https://pubmed.ncbi.nlm.nih.gov/35016921/

4. Yoneda, Mitsuhiro, Xu, Lei, Kajiyama, Hiroaki, Ward, Jerrold M, Kimura, Shioko. 2016. Secretoglobin Superfamily Protein SCGB3A2 Alleviates House Dust Mite-Induced Allergic Airway Inflammation in Mice. In International archives of allergy and immunology, 171, 36-44. doi:. https://pubmed.ncbi.nlm.nih.gov/27820933/