PRELP, or proline- and arginine-rich end leucine-rich repeat protein, is a small leucine-rich proteoglycan (SLRP). It binds type I collagen to basement membranes and type II collagen to cartilage, and is involved in processes like cell-cell adhesion, epithelial-to-mesenchymal transition (EMT), and collagen production. It is associated with signaling pathways such as wnt/β-catenin, NF-κB, FGF1/PI3K/AKT, and FAK/MAPK, and plays an important role in various biological processes and diseases [1,2,3,5,7,8,9]. Genetic models, especially knockout (KO) mouse models, are valuable for studying its functions.

In Prelp -/- mouse models, reduced cell-cell integrity of the blood-brain barrier was observed, with suppressed expression of adhesion junction proteins, indicating PRELP's role in regulating cell-cell adhesion in the neurovasculature [6]. In the context of diseases, in heart and liver fibrosis, Prelp was upregulated in chondrocyte-like myofibroblasts, and its knockdown reduced collagen expression, suggesting it promotes fibrosis [1]. In retinoblastoma, mRNA profiling of Prelp -/- mouse retina and Prelp-treated cells showed its contribution to cancer progression via regulating the microenvironment [2]. In colorectal cancer, although it was thought to be an inhibitor, it was found to be upregulated in metastatic tissues, promoting growth and metastasis by reducing cell stiffness and adhesion [4]. In oral squamous cell carcinoma, low Prelp expression was observed, and its upregulation inhibited cancer cell proliferation, invasion, and EMT via inactivation of the NF-κB pathway [5]. In acute myocardial infarction mouse models, over-expression of PRELP led to increased infarct size and interstitial fibrotic area through the wnt/β-catenin pathway [7]. In adipocytes, Prelp knockout in mice resisted high-fat diet-induced obesity, inhibited adipocyte differentiation, and alleviated adipose tissue fibrosis [9].

In conclusion, PRELP has diverse functions in different biological processes and disease conditions. Studies using KO mouse models have revealed its role in fibrosis, cancer progression, and maintaining tissue integrity. Understanding PRELP's functions provides potential therapeutic targets for diseases such as fibrosis, various cancers, and obesity-related metabolic disorders.

References:

1. Yamauchi, Yuto, Mieno, Hiroki, Suetsugu, Haruna, Watanabe, Hayato, Nakaya, Michio. 2024. Elevated PRELP expression in heart and liver fibrosis promotes collagen production. In Biochemical and biophysical research communications, 734, 150785. doi:10.1016/j.bbrc.2024.150785. https://pubmed.ncbi.nlm.nih.gov/39369540/

2. Hopkins, Jack, Asada, Ken, Leung, Alex, Sagoo, Mandeep S, Ohnuma, Shin-Ichi. 2022. PRELP Regulates Cell-Cell Adhesion and EMT and Inhibits Retinoblastoma Progression. In Cancers, 14, . doi:10.3390/cancers14194926. https://pubmed.ncbi.nlm.nih.gov/36230849/

3. Lewis, Marc. . PRELP, collagen, and a theory of Hutchinson-Gilford progeria. In Ageing research reviews, 2, 95-105. doi:. https://pubmed.ncbi.nlm.nih.gov/12437997/

4. Gui, Yajun, Deng, Xiangying, Li, Namei, Zhao, Lin. 2024. PRELP reduce cell stiffness and adhesion to promote the growth and metastasis of colorectal cancer cells by binding to integrin α5. In Experimental cell research, 441, 114151. doi:10.1016/j.yexcr.2024.114151. https://pubmed.ncbi.nlm.nih.gov/38992455/

5. Sun, Xiaoni, Chai, Luyi, Wang, Bingjie, Zhou, Jianbo. 2024. PRELP inhibits the progression of oral squamous cell carcinoma via inactivation of the NF-κB pathway. In Archives of oral biology, 167, 106068. doi:10.1016/j.archoralbio.2024.106068. https://pubmed.ncbi.nlm.nih.gov/39151326/

6. Davaapil, Hongorzul, Hopkins, Jack, Bonnin, Nadia, Sagoo, Mandeep S, Ohnuma, Shin-Ichi. 2023. PRELP secreted from mural cells protects the function of blood brain barrier through regulation of endothelial cell-cell integrity. In Frontiers in cell and developmental biology, 11, 1147625. doi:10.3389/fcell.2023.1147625. https://pubmed.ncbi.nlm.nih.gov/37936982/

7. Zhang, Yu, Fu, Chunli, Zhao, Shaohua, Li, Wei, Liu, Xiangju. 2022. PRELP promotes myocardial fibrosis and ventricular remodelling after acute myocardial infarction by the wnt/β-catenin signalling pathway. In Cardiovascular journal of Africa, 33, 228-233. doi:10.5830/CVJA-2022-001. https://pubmed.ncbi.nlm.nih.gov/35788244/

8. Li, Xiaoqing, Jiang, Zhongxiang, Li, Junfeng, Liu, Fuqiang, Jiang, Zheng. 2024. PRELP inhibits colorectal cancer progression by suppressing epithelial-mesenchymal transition and angiogenesis via the inactivation of the FGF1/PI3K/AKT pathway. In Apoptosis : an international journal on programmed cell death, 30, 16-34. doi:10.1007/s10495-024-02015-7. https://pubmed.ncbi.nlm.nih.gov/39242474/

9. Ding, Fei, Zheng, Peng, Yan, Xi-Yue, Zhang, Li, Yan, You-E. 2024. Adipocyte-secreted PRELP promotes adipocyte differentiation and adipose tissue fibrosis by binding with p75NTR to activate FAK/MAPK signaling. In International journal of biological macromolecules, 279, 135376. doi:10.1016/j.ijbiomac.2024.135376. https://pubmed.ncbi.nlm.nih.gov/39244119/