Hspg2, also known as heparan sulfate proteoglycan 2, encodes perlecan, a multifunctional proteoglycan. It preserves extracellular matrix integrity, controls signaling pathways, and influences many developmental processes, such as heart and brain formation, and is widely expressed in the musculoskeletal system [2]. It is involved in pathways like TNFSF13-NF-κB [1], and NID1/AKT [3].

In the context of hypertrophic scar, TNFSF13 binds to Hspg2 to activate the NF-κB signaling pathway, regulating the proliferation, migration, fibrosis, and inflammatory response of hypertrophic scar fibroblasts. MSC-exo can alleviate hypertrophic scar by inhibiting the TNFSF13/Hspg2 signaling pathway [1]. In bladder cancer, Hspg2 promotes tumor cell proliferation and chemotherapy resistance through the NID1/AKT signaling pathway [3]. In acute myeloid leukemia, Hspg2 overexpression is associated with poor prognosis [4]. In melanoma and non-small cell lung cancer, Hspg2 mutations are predictive of a better immune checkpoint inhibitor response [5]. Mutations in Hspg2 can also cause Schwartz-Jampel syndrome type 1, a rare musculoskeletal disorder [6].

In summary, Hspg2 plays essential roles in development, extracellular matrix maintenance, and various signaling pathways. Its dysregulation is associated with multiple diseases, including fibrotic, cancerous, and musculoskeletal disorders. Understanding Hspg2 through model-based research, such as the implications of its mutations and expression changes, can provide insights into disease mechanisms and potential therapeutic targets.

References:

1. Zhang, Huimin, Zang, Chengyu, Zhao, Wen, Wu, Jie, Cui, Rongtao. 2023. Exosome Derived from Mesenchymal Stem Cells Alleviates Hypertrophic Scar by Inhibiting the Fibroblasts via TNFSF-13/HSPG2 Signaling Pathway. In International journal of nanomedicine, 18, 7047-7063. doi:10.2147/IJN.S433510. https://pubmed.ncbi.nlm.nih.gov/38046235/

2. Martinez, Jerahme R, Dhawan, Akash, Farach-Carson, Mary C. 2018. Modular Proteoglycan Perlecan/HSPG2: Mutations, Phenotypes, and Functions. In Genes, 9, . doi:10.3390/genes9110556. https://pubmed.ncbi.nlm.nih.gov/30453502/

3. Li, Cong, Luo, Pengwei, Guo, Fengzhu, Wang, Shusen, Du, Ting. 2024. Identification of HSPG2 as a bladder pro-tumor protein through NID1/AKT signaling. In Cancer cell international, 24, 345. doi:10.1186/s12935-024-03527-7. https://pubmed.ncbi.nlm.nih.gov/39438949/

4. Zhou, Xiaojia, Liang, Simin, Zhan, Qian, Chi, Jianxiang, Wang, Li. 2020. HSPG2 overexpression independently predicts poor survival in patients with acute myeloid leukemia. In Cell death & disease, 11, 492. doi:10.1038/s41419-020-2694-7. https://pubmed.ncbi.nlm.nih.gov/32606327/

5. Zhang, Wenjing, Lin, Zhijuan, Shi, Fuyan, Wang, Suzhen, Wang, Qinghua. 2022. HSPG2 Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer. In Cancers, 14, . doi:10.3390/cancers14143495. https://pubmed.ncbi.nlm.nih.gov/35884556/

6. Brugnoni, Raffaella, Marelli, Daria, Iacomino, Nicola, Maggi, Lorenzo, Ardissone, Anna. 2023. Novel HSPG2 Gene Mutation Causing Schwartz-Jampel Syndrome in a Moroccan Family: A Literature Review. In Genes, 14, . doi:10.3390/genes14091753. https://pubmed.ncbi.nlm.nih.gov/37761893/