The discovery centers on the insulin-like growth factor (IGF) system, which drives cell differentiation, proliferation and survival while regulating nutrient metabolism. IGF-binding proteins, numbered IGFBP-1 through IGFBP-6, act as gatekeepers, controlling how much IGF-I and IGF-II reach their target receptors on cells.

In the bloodstream, IGFs pair with IGFBP-3 or IGFBP-5 and an acid-labile subunit, known as ALS, to create a large complex that stores the hormones for later use. This reservoir keeps IGF levels stable, the thesis explains. But the binding proteins do more than just hold IGFs. Post-translational tweaks, like heavy phosphorylation on IGFBP-1 during catabolic states such as fasting or illness, boost its grip on IGF-I and block the hormone’s effects.

Researchers found these novel proteases slice through the IGFBPs, likely altering their function. Such cleavage could free up IGFs or change how the proteins interact with cells and the extracellular matrix. The work highlights IGFBPs’ dual roles: they manage IGF activity and exert independent effects by latching onto cell surfaces or other molecules.

Take IGFBP-1’s C-terminal RGD sequence, for instance. That motif mimics patterns in extracellular proteins and binds integrin receptors on cell surfaces, influencing cell movement and adhesion without IGF involvement. The proteases target these sites, the study states, which might dial down those effects.

The thesis details lab methods to detect the enzymes. Using purified IGFBPs as bait, scientists tracked breakdown products via mass spectrometry and gel electrophoresis. They pinpointed the cleavage spots—specific peptide bonds in the protein chains—and tested conditions like pH and temperature that activate the proteases.

One key finding: these enzymes thrive in slightly acidic environments, common in inflamed tissues or tumors. That raises questions about their role in diseases tied to IGF dysregulation, from diabetes to cancer. Officials at Lund University’s medical faculty called the characterization a step forward for understanding IGFBP turnover.

Earlier studies showed generic proteases like matrix metalloproteinases nibble at IGFBPs, but these new ones appear specialized. The thesis reports they ignore other proteins, focusing solely on IGFBPs-1 through -6. Inhibitors blocked their action, confirming specificity.

Phosphorylation matters too. Highly modified IGFBP-1 resisted cleavage less than its basic form, suggesting catabolic states might prolong its inhibitory power on IGF-I. The researchers propose these proteases help fine-tune IGF availability during stress.

In cell cultures, adding the proteases boosted IGF signaling, as measured by downstream markers like Akt phosphorylation. That hints at therapeutic angles: enhancing protease activity could counter IGFBP-1’s brakes in conditions like poor wound healing.

The work builds on decades of IGF research. Since the 1980s, scientists have mapped the system’s components, but proteolytic control remained murky. This thesis fills gaps by isolating the enzymes from human plasma and tissue extracts.

Future steps include sequencing the proteases for identity and developing assays for patient samples. The findings could guide drug design targeting IGF pathways in metabolic disorders or growth-related cancers, according to the report.

Lund University presented the thesis on an unspecified date in its avhandlingar.se database, marking a fresh look at an old system.