PhD Scientific Days 2024

Pathological and Oncological Sciences I.

Role of SPOCK1 Proteoglycan in Regenerating Human and Rat Livers

Text of the abstract

Introduction
Acute and chronic liver injuries can trigger a wide range of signaling that can lead to liver regeneration and restoration of the functional liver tissue. In human and rat livers this is achieved either by hepatocyte proliferation or by regeneration from progenitor cells. Previous papers identified changes in several non-structural ECM proteins during liver regeneration, although we lack mechanistic details. SPOCK1 is a chondroitin sulfate-heparan sulfate proteoglycan and previous studies showed that promotes proliferation and invasion of different types of cancer.
Aims
The aim of the current study is to identify the mechanistic details of how SPOCK is involved in liver regeneration and to decipher the underlying signaling pathways.
Methods
We used human liver samples and animal models for our studies.
We performed IHC staining of SPOCK1 on peritumoral normal human liver tissues (n=2) also on explanted human livers due to massive hepatic necrosis with two distinct regenerative pattern: 1) regeneration from dedifferentiated hepatocytes (n=5); 2) regeneration trough progenitor cells forming regenerative nodules (n=3). In our regenerative animal model, we performed traditional 70% partial hepatectomy on F344 rats, then sacrificed them at 48 (n=3) and 96 hour (n=3) when liver and serum samples were collected. We analyzed SPOCK1 expression in the liver by Western Blotting and RT-qPCR, we also quantified SPOCK1 concentration in the serum samples by Dot Blot.
Result
SPOCK1 IHC showed diffuse faint positive expression human control samples, also intense granular pattern in hepatocytes localized around the central veins or found randomly in the parenchyma. Interestingly, we didn’t see an increase in SPOCK1 expression in regenerating human liver samples. They showed diffuse intracellular positivity, and the granular pattern of the staining was less prominent. Compared to the control samples our early liver regeneration model revealed decreased SPOCK1 concentration in the liver at 24 and 48h after partial hepatectomy. Surprisingly we observed the opposite trend in the serum samples of the corresponding groups.
Conclusion
The interesting dynamic of SPOCK1 seen in our animal model and in human samples raises the possibility that this proteoglycan actively participates in liver regeneration.
Funding
ÚNKP-23-3-II-SE-77, FK-OTKA 138673, FK-OTKA 138593