Fmod, short for Fibromodulin, is an archetypal member of the class II small leucine-rich proteoglycan family. It plays crucial roles in various biological processes. By binding to extracellular matrix components like collagen and lysyl oxidase, it regulates collagen-related processes such as cross-linking, packing, and fibril architecture. As a pluripotent molecule, it interacts with cytokines and growth factors, especially those in the TGF-β superfamily, influencing cell adhesion, proliferation, migration, and more. It has promigratory, proangiogenic, anti-inflammatory, and antifibrogenic properties and is involved in cell fate determination, progenitor cell recruitment, and tissue regeneration [4].

In terms of disease-related findings, FMOD levels were decreased in TBI patients' serum, and its overexpression alleviated depression-like behaviors potentially through the PI3K/AKT/mTOR signaling pathway [1]. In chronic lymphocytic leukemia (CLL), FMOD is almost exclusively expressed in lymphocytes, and its quantification may aid in diagnosing complex lymphoproliferative disorders [2]. In non-small cell lung cancer cell line H322, silencing FMOD reduces cell proliferation, adhesion, and migration, likely by inhibiting the TGF-β/Smad signaling pathway [3]. Also, silencing of FMOD and ROR1 in CLL cells led to apoptosis [5].

In conclusion, Fmod is a multifunctional gene involved in regulating extracellular matrix and cell-related processes. Research using models such as gene silencing in cell lines has revealed its potential roles in diseases like TBI-related depression, lymphoproliferative disorders, and lung and leukemia cancers, highlighting its importance as a potential therapeutic target and biomarker.

References:

1. Huang, Xuekang, Zhu, Ziyu, Du, Mengran, Liu, Lian, Liao, Z B. 2024. FMOD Alleviates Depression-Like Behaviors by Targeting the PI3K/AKT/mTOR Signaling After Traumatic Brain Injury. In Neuromolecular medicine, 26, 24. doi:10.1007/s12017-024-08793-2. https://pubmed.ncbi.nlm.nih.gov/38864941/

2. Sorigue, Marc, Junca, Jordi, Ferra, Christelle, Beà, Silvia, Zamora, Lurdes. 2020. FMOD expression in whole blood aids in distinguishing between chronic lymphocytic leukemia and other leukemic lymphoproliferative disorders. A pilot study. In Cytometry. Part B, Clinical cytometry, 98, 421-428. doi:10.1002/cyto.b.21890. https://pubmed.ncbi.nlm.nih.gov/32530577/

3. Gu, Hai-Bo, Sun, Li, Liu, Yang-Xiang, Li, Ning. . [Effect of Silencing FMOD on Proliferation and Migration of H322 Cells and Its Mechanism]. In Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition, 51, 165-170. doi:10.12182/20200360603. https://pubmed.ncbi.nlm.nih.gov/32220183/

4. Zheng, Z, Granado, H S, Li, C. 2022. Fibromodulin, a Multifunctional Matricellular Modulator. In Journal of dental research, 102, 125-134. doi:10.1177/00220345221138525. https://pubmed.ncbi.nlm.nih.gov/36515321/

5. Choudhury, Aniruddha, Derkow, Katja, Daneshmanesh, Amir Hossein, Osterborg, Anders, Mellstedt, Håkan. 2010. Silencing of ROR1 and FMOD with siRNA results in apoptosis of CLL cells. In British journal of haematology, 151, 327-35. doi:10.1111/j.1365-2141.2010.08362.x. https://pubmed.ncbi.nlm.nih.gov/20813009/