Rgs1-KO Mouse

Rgs1, short for Regulator of G-protein signaling 1, is involved in regulating G-protein-coupled receptor (GPCR) signaling. By accelerating the hydrolysis of GTP to GDP on the Gα subunit of heterotrimeric G-proteins, it turns off GPCR-mediated signaling pathways. This regulation is crucial for various cellular processes such as cell communication, signal transduction, and cell response to stimuli [7].

In acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and pulmonary fibrosis (PF), epithelium-and endothelium-derived exosomes target RGS1, which coregulates the immunophenotype of alveolar macrophage subpopulations through the PLC-IP3R signal-dependent intracellular Ca2+ response. Imbalance of alveolar macrophages due to lack of relevant exosome secretion is related to these diseases, and treatment with exosomes can improve the conditions [1]. In renal interstitial fibrosis (RIF), RGS1 expression is elevated. Knockdown of RGS1 inhibits renal cell inflammatory response, fibrosis, and renal fibrosis in RIF mice, suggesting it as a potential therapeutic target [2]. In cervical cancer, RGS1 is an oncogenic gene affecting the immune microenvironment, and its knockdown can inhibit cell proliferation, migration, invasion, and tumor growth in nude mice [3]. In gastric cancer, silencing the RGS1 gene reduces the proliferation of drug-resistant cells in vitro and inhibits tumor growth in vivo, serving as an antitumor target [4]. In osteosarcoma, RGS1 is a tumor-promoting gene, and microRNA-376b-3p can target it to inhibit cell proliferation, metastasis, and apoptosis [6]. In spinal cord injury, RGS1 knockdown suppresses TLR-signaling-pathway-induced inflammation, inhibits MMP-induced tissue degradation, and improves spinal cord histology and function recovery [5].

In summary, Rgs1 plays diverse roles in multiple biological processes and disease conditions. Through gene-knockout (KO) or conditional-knockout (CKO) mouse models and other loss-of-function experiments, it has been revealed that Rgs1 is involved in immune regulation, fibrosis, and tumor-related processes. These findings provide potential therapeutic strategies for diseases like ALI/ARDS, PF, RIF, cervical cancer, gastric cancer, osteosarcoma, and spinal cord injury.

References:

1. Feng, Zunyong, Zhou, Jing, Liu, Yinhua, Wang, Yongsheng, Xia, Hongping. 2021. Epithelium- and endothelium-derived exosomes regulate the alveolar macrophages by targeting RGS1 mediated calcium signaling-dependent immune response. In Cell death and differentiation, 28, 2238-2256. doi:10.1038/s41418-021-00750-x. https://pubmed.ncbi.nlm.nih.gov/33753901/

2. Lu, Tefei, Chen, Sheng, Xu, Jianting. 2023. RGS1 mediates renal interstitial fibrosis through activation of the inflammatory response. In Archives of biochemistry and biophysics, 750, 109744. doi:10.1016/j.abb.2023.109744. https://pubmed.ncbi.nlm.nih.gov/37696381/

3. Zhang, Siyang, Wang, Han, Liu, Jiao, Zeng, Zhi, Wang, Min. 2022. RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation. In Journal of translational medicine, 20, 334. doi:10.1186/s12967-022-03526-0. https://pubmed.ncbi.nlm.nih.gov/35879796/

4. Chen, Zhixiong, Liu, Banglun, Zhang, Shouru, Lv, Yuyu, Sun, Hao. 2022. RGS1 serves as an antitumor target to inhibit proliferation of NICN87-DR cells and tumor growth in the gastric cancer mouse model. In Turkish journal of biology = Turk biyoloji dergisi, 46, 277-287. doi:10.55730/1300-0152.2616. https://pubmed.ncbi.nlm.nih.gov/37529094/

5. Feng, Dongqian, Yu, Jiasheng, Bao, Lei, Fan, Daobo, Zhang, Bin. 2021. Inhibiting RGS1 attenuates secondary inflammation response and tissue degradation via the TLR/TRIF/NF-κB pathway in macrophage post spinal cord injury. In Neuroscience letters, 768, 136374. doi:10.1016/j.neulet.2021.136374. https://pubmed.ncbi.nlm.nih.gov/34852285/

6. Zhang, Lei, Yao, Meng, Ma, Weikang, Jiang, Yongqing, Wang, Wenbo. . MicroRNA-376b-3p targets RGS1 mRNA to inhibit proliferation, metastasis, and apoptosis in osteosarcoma. In Annals of translational medicine, 9, 1652. doi:10.21037/atm-21-4949. https://pubmed.ncbi.nlm.nih.gov/34988161/

7. Liu, Tiezhu, Huang, Tao, Li, Jiajia, Wang, Shiwen, Liang, Mifang. 2023. Optimization of differentiation and transcriptomic profile of THP-1 cells into macrophage by PMA. In PloS one, 18, e0286056. doi:10.1371/journal.pone.0286056. https://pubmed.ncbi.nlm.nih.gov/37459313/