Pigr-KO Mouse

Pigr, short for Polymeric immunoglobulin receptor, is a transmembrane transporter responsible for the translocation of polymeric IgA across the intestinal epithelium [1,3,4]. It is crucial for mucosal immunity as it also serves as the precursor of secretory component which enhances SIgA immune functions [6]. Its role in mucosal immunity and related pathways makes it an important gene in maintaining the body's defense mechanisms against pathogens [6]. Genetic models, such as KO mouse models, can be valuable in studying its functions.

In ethanol-induced liver disease, pIgR-deficient (pIgR-/-) mice showed increased liver injury, steatosis, inflammation, plasma lipopolysaccharide levels, and hepatic bacteria, indicating elevated bacterial translocation compared to wild-type littermates [3]. Re-expressing pIgR in pIgR-/-mice via adeno-associated virus serotype 8 (AAV8) increased intestinal IgA levels and ameliorated ethanol-induced steatohepatitis by reducing bacterial translocation [3]. In hepatocellular carcinoma (HCC), circulating EVs from patients with late-stage HCC had elevated pIgR expression. Blocking EV-pIgR with an anti-pIgR antibody hindered the augmenting effect of these EVs on cancer stemness and tumorigenesis, suggesting EV-pIgR activates PDK1/Akt/GSK3β/β-catenin signaling cascades [2]. Also, in HCC, PIGR was overexpressed in tumors and associated with poor disease-free survival. RNAseq analysis indicated PIGR might promote cancer development in HCC by activating the ribosome pathway [5].

In conclusion, Pigr plays essential roles in mucosal immunity, especially in the transport of IgA. Through gene-knockout mouse models, its functions in preventing ethanol-induced liver disease by limiting bacterial translocation have been revealed. In cancer, especially HCC, it seems to be involved in promoting cancer stemness, tumorigenesis, and is associated with recurrence, highlighting its potential as a therapeutic target in these disease areas [2,3,5].

References:

1. Chae, Jisu, Choi, Jinny, Chung, Junho. 2023. Polymeric immunoglobulin receptor (pIgR) in cancer. In Journal of cancer research and clinical oncology, 149, 17683-17690. doi:10.1007/s00432-023-05335-4. https://pubmed.ncbi.nlm.nih.gov/37897659/

2. Tey, Sze Keong, Wong, Samuel Wan Ki, Chan, Janice Yuen Tung, Yun, Jing Ping, Yam, Judy Wai Ping. 2021. Patient pIgR-enriched extracellular vesicles drive cancer stemness, tumorigenesis and metastasis in hepatocellular carcinoma. In Journal of hepatology, 76, 883-895. doi:10.1016/j.jhep.2021.12.005. https://pubmed.ncbi.nlm.nih.gov/34922977/

3. Hendrikx, Tim, Lang, Sonja, Rajcic, Dragana, Mikulski, Zbigniew, Schnabl, Bernd. 2023. Hepatic pIgR-mediated secretion of IgA limits bacterial translocation and prevents ethanol-induced liver disease in mice. In Gut, 72, 1959-1970. doi:10.1136/gutjnl-2022-328265. https://pubmed.ncbi.nlm.nih.gov/36690432/

4. Keyt, Bruce A, Baliga, Ramesh, Sinclair, Angus M, Carroll, Stephen F, Peterson, Marvin S. 2020. Structure, Function, and Therapeutic Use of IgM Antibodies. In Antibodies (Basel, Switzerland), 9, . doi:10.3390/antib9040053. https://pubmed.ncbi.nlm.nih.gov/33066119/

5. Zhang, Yuan, Zhang, Jijie, Chen, Xiaorong, Yang, Zongguo. 2021. Polymeric immunoglobulin receptor (PIGR) exerts oncogenic functions via activating ribosome pathway in hepatocellular carcinoma. In International journal of medical sciences, 18, 364-371. doi:10.7150/ijms.49790. https://pubmed.ncbi.nlm.nih.gov/33390805/

6. Johansen, F-E, Kaetzel, C S. 2011. Regulation of the polymeric immunoglobulin receptor and IgA transport: new advances in environmental factors that stimulate pIgR expression and its role in mucosal immunity. In Mucosal immunology, 4, 598-602. doi:10.1038/mi.2011.37. https://pubmed.ncbi.nlm.nih.gov/21956244/