MFAP4: A pivotal extracellular matrix target for managing tissue fibrosis, cardiovascular remodeling, and cancer.

• Gene Information: MFAP4 (microfibrillar-associated protein 4) is an extracellular matrix glycoprotein belonging to the fibrinogen-like domain superfamily, which is encoded on human chromosome 17.
•  Protein Expression: MFAP4 is predominantly secreted into elastic fiber-rich tissues such as lungs, heart, and blood vessels. It is significantly upregulated in fibrotic organs and remodeling tumor microenvironments, serving as a promising diagnostic biomarker and therapeutic target for tissue remodeling.
• Signaling Pathway: Upon binding to cell-surface integrins (such as αvβ3 and αvβ5) and extracellular matrix components, MFAP4 activates downstream FAK, AKT, and ERK1/2 phosphorylation cascades. This signaling drives vascular smooth muscle cell migration, fibroblast activation, matrix deposition, and pathogenic tissue remodeling.
• Therapeutic Inhibition: MFAP4 is an attractive target for therapeutic monoclonal antibodies and targeted inhibitors. Neutralizing extracellular MFAP4 blocks integrin-mediated signaling, effectively attenuating organ fibrosis, pathological vascular remodeling, and tumor progression, offering significant therapeutic potential across fibrotic and metabolic diseases.

MFAP4

• The whole mouse Mfap4 gene include the promoter, 5’UTR, the whole molecule (ATG to STOP codon) and 3’UTR were replaced by humancounterparts in B-hMFAP4 mice.

Strain specific analysis of MFAP4 mRNA expression in wild-type C57BL/6JNifdc mice and homozygous B-hMFAP4 mice by RT-PCR. Lung RNA was isolated fromwild-type C57BL/6JNifdc mice (+/+) and homozygous B-hMFAP4 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR withmouse or human MFAP4 primers. Sequencing of the PCR products confirmed that the amplified sequences were consistent with databasereference sequences.

Strain specific MFAP4 expression analysis in homozygous B-hFAP4 mice by Western blot. The kidney, lung, bladder, ovary and uterus samples were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hMFAP4 mice (H/H) and then analyzed by western blot with anti-MFAP4 antibody (abcam, ab169757). 40 μg total proteins were loaded for western blotting analysis. MFAP4 protein was detected in the lung, bladder, ovary and uterus of wild-type C57BL/6JNifdc mice and homozygous B-hMFAP4 mice, as the antibody is cross-recognize both human and mouse MFAP4.