CTRP-Familie

The C1q/TNF-related proteins (CTRP) form a family of secreted proteins that are structurally related to the complement factor C1q and the cytokine tumor necrosis factor-α (TNF-α). Their main role is in anti-inflammatory activation, insulin sensitization and regulation of blood lipids. The family comprises at least 15 members in humans: CTRP1 to CTRP15 (including adiponectin, also known as CTRP1. CTRP proteins are characterized by the following structural features:

• Signal peptide: For secretion into the extracellular space.
• Variable region: At the N-terminal end.
• Collagen-like domain: Enables oligomerization (e.g. trimer, hexamer formation).
• Globular C1q domain: This region is crucial for biological activity, similar to that of TNF family members.

CTRP1(adiponectin): Regulates glucose and lipid metabolism. Increases insulin sensitivity.

CTRP3, CTRP9: Promotes insulin action and glucose uptake in target tissues. CTRP-3 (C1q/TNF-related protein-3) belongs to the family of C1q/TNF-related proteins that counteract the effects of lipopolysaccharide (LPS). CTRP-3 is synthesized and secreted by MAT (mesenteric adipose tissue). This adipokine significantly and dose-dependently reduced LPS-induced IL-8 secretion in CLPF within 8 hours after LPS exposure, while LPS-induced interleukin-6 and TNF release were not affected. CTRP-3 inhibited TGF-β production and the expression of CTGF and collagen I in CLPF, while collagen III expression remained unchanged.

CTRP5: Involved in lipid metabolism and possibly age-related macular degeneration.

Inflammation and immunomodulation

• Some CTRPs have an anti-inflammatory effect (e.g. CTRP3, CTRP9) by inhibiting NF-κB signaling. Other CTRPs such as CTRP1 can induce pro-inflammatory cytokines.

Cardiovascular system

• CTRP9: Exerts a protective effect on the heart by promoting vasodilation and inhibiting cardiac fibrosis.
• CTRP3: Protects against myocardial fibrosis and post-infarction inflammation.

Other functions

• CTRP6 and CTRP8: Involved in cellular differentiation, autophagy, tumor biology.
• CTRP6: Possible role in fibrosis and in certain types of cancer (e.g. glioblastoma, gastric cancer).