Organ fibrosis is defined as a deregulated wound-healing process characterized by a progressive accumulation of fibrous tissue and by reduced remodeling that can lead to the loss of functionality of the affected organ. This pathological process is quite common in several parenchymal organs such as kidneys, liver, and lungs and represents a real health emergency in developed western countries since a real anti-fibrotic therapy is not yet available in most cases. Heparanase (HPSE), which is the enzyme that cuts off the side chains of heparan sulfate (HS) proteoglycan, appears to be involved in the aetiopathogenesis of fibrosis in all these organs, even if with different mechanisms. Here we discuss how the interplay between HPSE and components of the immune and inflammatory responses can activate recruitment, proliferation, and activation of myofibroblasts which represent the main cell type responsible for the deposition of fibrous matrix. Finally, bearing in mind that once the activity of HPSE is inhibited no other molecule is able to perform the same function, it is desirable that this enzyme could prove to be a suitable pharmacological target in anti-fibrotic therapy.

Impact of Heparanse on Organ Fibrosis

Gambaro, Giovanni;
2020-01-01

Abstract

Organ fibrosis is defined as a deregulated wound-healing process characterized by a progressive accumulation of fibrous tissue and by reduced remodeling that can lead to the loss of functionality of the affected organ. This pathological process is quite common in several parenchymal organs such as kidneys, liver, and lungs and represents a real health emergency in developed western countries since a real anti-fibrotic therapy is not yet available in most cases. Heparanase (HPSE), which is the enzyme that cuts off the side chains of heparan sulfate (HS) proteoglycan, appears to be involved in the aetiopathogenesis of fibrosis in all these organs, even if with different mechanisms. Here we discuss how the interplay between HPSE and components of the immune and inflammatory responses can activate recruitment, proliferation, and activation of myofibroblasts which represent the main cell type responsible for the deposition of fibrous matrix. Finally, bearing in mind that once the activity of HPSE is inhibited no other molecule is able to perform the same function, it is desirable that this enzyme could prove to be a suitable pharmacological target in anti-fibrotic therapy.
2020
Acute kidney injury
Epithelial mesenchymal transition
Extracellular matrix
Fibrosis
Transforming growth factor beta
Fibrosis
Glucuronidase
Heparan Sulfate Proteoglycans
Humans
Myofibroblasts
Organ Specificity
Wound Healing
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1101977
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