PLG: Key Plasminogen Precursor & Fibrinolytic Therapeutic Target

• Gene Information: Encoded by the PLG gene on chromosome 6q26, a member of the plasminogen serine protease family.
•  Protein Expression: Predominantly synthesized in liver and secreted into plasma, dynamically binding to cell-surface plasminogen receptors (Plg-R’s) on various somatic cells. 
• Signaling Pathway: Activated by u-PA/t-PA to generate plasmin responsible for fibrin degradation, while plasminogen-Plg-R interaction modulates immunity, tissue repair and angiogenesis; the proteolytic cascade is negatively regulated by PAI-1/2, TAFI, TXA and EACA. 
• Therapeutic Inhibition: PLG inhibitors and PLG-targeted nucleic acid drugs block plasminogen synthesis or plasmin activity to restrain hyperfibrinolysis, emerging as promising agents for coagulation and bleeding disorders, while plasminogen supplementation is applied for thrombolysis and tissue repair.

• The exons 1~19 of mouse Plg gene that encode the whole molecule (ATG to STOP codon) were replaced by human counterparts in B-hPLG mice. 
• The promoter, 5’UTR and 3’UTR region of the mouse gene are replaced by the promoter, 5’UTR and 3’UTR region of human gene.

Strain specific analysis of PLG mRNA expression in wild-type C57BL/6JNifdc and B-hPLG mice by RT-PCR. Liver RNA were isolated from wild-type C57BL/6JNifdc mice (+/+) and heterozygous B-hPLG mice (H/+), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human PLG primers.

Human PLG protein expression analysis in heterozygous B-hPLG mice by ELISA. Plasma were collected from female C57BL/6JNifdc mice (+/+, male) and heterozygous B-hPLG mice (H/+, male). Protein expression level of hPLG was analyzed by ELISA with anti-PLG kit (Abcam, ab108893). Values are expressed as mean ± SEM. ND: Not Detectable.