Rcn3, also known as Reticulocalbin 3, is an endoplasmic reticulum (ER) lumen-residing Ca2+ binding protein belonging to the CREC family. It is located in the secretory pathway of living cells and plays an essential role in protein biosynthesis processes via this pathway [2,3].

In vivo studies using gene knockout models have revealed significant functions of Rcn3. In a fibroblast-selective knockdown mouse model, repressing Rcn3 expression ameliorated bleomycin-induced lung fibrosis and pulmonary dysfunction. Mechanistically, RCN3 promotes fibroblast activation through a TGFβ1-RCN3-TGFBR1 positive feedback loop, upregulating TGFBR1 expression [1]. In a type II alveolar epithelial cell (AECIIs) specific Rcn3 conditional knockout (CKO) mouse model, the selective ablation of Rcn3 in AECIIs significantly alleviated the severity of porcine pancreatic elastase-induced emphysema [4].

In conclusion, Rcn3 is crucial in protein biosynthesis and is involved in regulating processes related to lung-associated diseases. The Rcn3 knockout and CKO mouse models have been instrumental in uncovering its role in pulmonary fibrosis and emphysema, providing insights into potential therapeutic targets for these diseases.

References:

1. Wu, Mingting, Wang, Zhenyan, Shi, Xiaoqian, Ma, Yingmin, Jin, Jiawei. 2023. TGFβ1-RCN3-TGFBR1 loop facilitates pulmonary fibrosis by orchestrating fibroblast activation. In Respiratory research, 24, 222. doi:10.1186/s12931-023-02533-z. https://pubmed.ncbi.nlm.nih.gov/37710230/

2. Hou, Yu, Li, Yongchao, Gong, Fuxing, Fang, Qiuhong, Ma, Runlin Z. . A Preliminary Study on RCN3 Protein Expression in Non-small Cell Lung Cancer. In Clinical laboratory, 62, 293-300. doi:. https://pubmed.ncbi.nlm.nih.gov/27156316/

3. He, Yi, Alejo, Salvador, Johnson, Jessica D, Jayamohan, Sridharan, Sareddy, Gangadhara R. 2023. Reticulocalbin 3 Is a Novel Mediator of Glioblastoma Progression. In Cancers, 15, . doi:10.3390/cancers15072008. https://pubmed.ncbi.nlm.nih.gov/37046668/

4. Zhang, Qianyu, Wang, Tong, Jin, Jiawei, Z Ma, Runlin, Fang, Qiuhong. 2021. Rcn3 Suppression Was Responsible for Partial Relief of Emphysema as Shown by Specific Type II Alveolar Epithelial Cell Rcn3 CKO Mouse Model. In International journal of chronic obstructive pulmonary disease, 16, 147-158. doi:10.2147/COPD.S272711. https://pubmed.ncbi.nlm.nih.gov/33531801/