Postn-KO Mouse

Postn, also known as periostin, is a protein-coding gene. The protein it encodes is involved in multiple biological processes, such as extracellular matrix remodeling, and is associated with signaling pathways like Wnt/β-catenin and NF-κB. It plays a crucial role in various physiological and pathological conditions, including tumor development, fibrosis, and tissue degeneration [3,6,8]. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying its functions.

In cancer, POSTN + cancer-associated fibroblasts (CAFs) act as immune response barriers, hindering T-cell infiltration and reducing immunotherapy efficacy in hepatocellular carcinoma and non-small cell lung cancer [1,2]. In gastric cancer, POSTN secreted by extracellular matrix CAFs promotes macrophage chemotaxis via the Akt signaling pathway, leading to immune checkpoint blockade resistance [10]. In acne keloidalis, communication between POSTN + fibroblasts and SPP1 + myeloid cells via the SPP1 axis contributes to fibrotic scarring [5]. In idiopathic pulmonary fibrosis, POSTN is a dysregulated hub gene, and its knockdown attenuates fibrotic marker expression [6]. In neuroblastoma, ALK drives tumorigenesis in part through a feedforward loop between POSTN and WNT signaling [7]. In intervertebral disc degeneration, POSTN promotes nucleus pulposus cell senescence and extracellular matrix metabolism via the Wnt/β-catenin and NF-κB signaling pathways, and its inhibition can ameliorate the disease progression [8]. In heart failure, FAP/POSTN fibroblasts emerge due to interactions between CCR2 macrophages and fibroblasts mediated by IL-1β signalling, and targeting this reduces myocardial fibrosis and improves cardiac function [9]. In prurigo nodularis, dysregulated POSTN + WNT5A + fibroblast subpopulations may predispose to cancer-associated FB-associated malignancies [4].

In conclusion, Postn plays essential roles in multiple biological processes and disease conditions, especially in tumor-related immune evasion, fibrosis, and tissue-specific degenerative diseases. Studies using KO/CKO mouse models have significantly enhanced our understanding of Postn's functions, providing potential therapeutic targets for these diseases.

References:

1. Wang, Hao, Liang, Yuan, Liu, Zheng, Zhao, Haitao, Lu, Ling. 2024. POSTN+ cancer-associated fibroblasts determine the efficacy of immunotherapy in hepatocellular carcinoma. In Journal for immunotherapy of cancer, 12, . doi:10.1136/jitc-2023-008721. https://pubmed.ncbi.nlm.nih.gov/39067872/

2. Chen, Chao, Guo, Qiang, Liu, Yang, Liu, Jixian, Xu, Qumiao. . Single-cell and spatial transcriptomics reveal POSTN+ cancer-associated fibroblasts correlated with immune suppression and tumour progression in non-small cell lung cancer. In Clinical and translational medicine, 13, e1515. doi:10.1002/ctm2.1515. https://pubmed.ncbi.nlm.nih.gov/38115703/

3. Yu, Yue, Tan, Chang-Ming, Jia, Yuan-Yuan. 2021. Research status and the prospect of POSTN in various tumors. In Neoplasma, 68, 673-682. doi:10.4149/neo_2021_210223N239. https://pubmed.ncbi.nlm.nih.gov/34348466/

4. Patel, Jay R, Joel, Marina Z, Lee, Kevin K, Kang, Sewon, Kwatra, Shawn G. 2024. Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis. In The Journal of investigative dermatology, 144, 1568-1578.e5. doi:10.1016/j.jid.2023.12.021. https://pubmed.ncbi.nlm.nih.gov/38246584/

5. Hong, Yi-Kai, Hwang, Daw-Yang, Yang, Chao-Chun, McGrath, John A, Hsu, Chao-Kai. 2024. Profibrotic Subsets of SPP1+ Macrophages and POSTN+ Fibroblasts Contribute to Fibrotic Scarring in Acne Keloidalis. In The Journal of investigative dermatology, 144, 1491-1504.e10. doi:10.1016/j.jid.2023.12.014. https://pubmed.ncbi.nlm.nih.gov/38218364/

6. Wu, Shufei, Liu, Mengying, Zhang, Mingrui, Huang, Xinmei, Cao, Mengshu. 2024. The gene expression of CALD1, CDH2, and POSTN in fibroblast are related to idiopathic pulmonary fibrosis. In Frontiers in immunology, 15, 1275064. doi:10.3389/fimmu.2024.1275064. https://pubmed.ncbi.nlm.nih.gov/38370408/

7. Huang, Miller, Fang, Wanqi, Farrel, Alvin, Maris, John M, Weiss, William A. 2024. ALK upregulates POSTN and WNT signaling to drive neuroblastoma. In Cell reports, 43, 113927. doi:10.1016/j.celrep.2024.113927. https://pubmed.ncbi.nlm.nih.gov/38451815/

8. Zhu, Daxue, Chen, Shijie, Sheng, Pan, Li, Yanhu, Kang, Xuewen. 2024. POSTN promotes nucleus pulposus cell senescence and extracellular matrix metabolism via activing Wnt/β-catenin and NF-κB signal pathway in intervertebral disc degeneration. In Cellular signalling, 121, 111277. doi:10.1016/j.cellsig.2024.111277. https://pubmed.ncbi.nlm.nih.gov/38944256/

9. Amrute, Junedh M, Luo, Xin, Penna, Vinay, Ason, Brandon, Lavine, Kory J. 2024. Targeting immune-fibroblast cell communication in heart failure. In Nature, 635, 423-433. doi:10.1038/s41586-024-08008-5. https://pubmed.ncbi.nlm.nih.gov/39443792/

10. You, Tingting, Tang, Hui, Wu, Wenjing, Sun, Zhao, Zhao, Robert Chunhua. 2023. POSTN Secretion by Extracellular Matrix Cancer-Associated Fibroblasts (eCAFs) Correlates with Poor ICB Response via Macrophage Chemotaxis Activation of Akt Signaling Pathway in Gastric Cancer. In Aging and disease, 14, 2177-2192. doi:10.14336/AD.2023.0503. https://pubmed.ncbi.nlm.nih.gov/37199594/