The multifaceted roles of perlecan in fibrosis

Abstract

Perlecan, or heparan sulfate proteoglycan 2 (HSPG2), is a ubiquitous heparan sulfate proteoglycan that has major roles in tissue and organ development and wound healing by orchestrating the binding and signaling of mitogens and morphogens to cells in a temporal and dynamic fashion. In this review, its roles in fibrosis are reviewed by drawing upon evidence from tissue and organ systems that undergo fibrosis as a result of an uncontrolled response to either inflammation or traumatic cellular injury leading to an over production of a collagen-rich extracellular matrix. This review focuses on examples of fibrosis that occurs in lung, liver, kidney, skin, kidney, neural tissues and blood vessels and its link to the expression of perlecan in that particular organ system.

A Biomimetic Approach toward Enhancing Angiogenesis: Recombinantly Expressed Domain V of Human Perlecan Is a Bioactive Molecule That Promotes Angiogenesis and Vascularization of Implanted Biomaterials

“…In addition to the utility of its GAG chains in growth factor signaling, rDV and other proteoglycans carry additional functionalities in their protein core. [ 6 ] Perlecan protein core plays a major role in ECM and cell interactions, [ 21 ] with the endothelial cell α 2 β 1 integrin binding site is found in domain V. The protein core also provides a range of easily accessible chemistries that allow rDV to be immobilized on biomaterials such as silk. rDV immobilization can have a major effect on its presentation and function, as was demonstrated when rDV was immobilized on silk films.…”

“…An α 2 β 1 integrin binding site (●) is present on domain V and supports endothelial cell binding. [ 21 ] B) Schematic representation of recombinantly expressed rDV. rDV is expressed by HEK‐293 cells as a mixed protein population consisting of an 80 kDa protein decorated with a single HS or CS GAG chain, and contains the integrin binding site (●).…”

AGO HITS-CLIP in Adipose Tissue Reveals miR-29 as a Post-Transcriptional Regulator of Leptin

“…In heart, miR-29 suppresses fibrosis by targeting Col3a1, Fbn1 , and Eln 24 . These 3 genes, among several others including Hspg2 and Cflar , are fibrosis-related miR-29 targets in adipose tissue 40,41 . Future in vivo studies, carried out in both lean and obese mice, are needed to fully explore the physiological role of miR-29 in these pathways.…”

Análise do efeito do gene Hspg2 na variabilidade dos fenótipos esquelético e vascular da Sí­ndrome de Marfan

“…Ela apresenta 5 domínios, sendo o primeiro um sítio exclusivo, responsável pela ligação a glicosaminoglicanos. Esses podem ser condroitina-sulfato e/ou querato-sulfato, como observado em células epiteliais e de músculo liso, ou, heparano-sulfato, como é o caso de células endoteliais (CHUANG et al, 2010;KNOX et al, 2005;LORD et al, 2014LORD et al, , 2018. Além disso, perlecan possui sítios de clivagem para uma série de proteínas presentes na matriz como plasmina, trombina e colagenases (Figura 5).…”

“…Por meio de suas cadeias de heparano-sulfato, perlecan sequestra lipoproteínas, como por exemplo, lipoproteínas de baixa densidade, moléculas-chave na aterogênese (PILLARISETTI et al, 1997;XU et al, 2015). Apesar dos efeitos próaterogênicos de perlecan, é a falta da expressão de perlecan nos estágios iniciais da doença que permite a ativação e proliferação das CMLV, bem como o processo de síntese de MEC (KINSELLA et al, 2003;LORD et al, 2018;TRAN-LUNDMARK et al, 2008). Isso ocorre porque os níveis de perlecan em CMLVs senescentes e diferenciadas é maior em comparação ao encontrado em células proliferativas, indicando que esta proteína atua como um potente inibidor de proliferação de CMLVs.…”