Endostatin in fibrosis and as a potential candidate of anti-fibrotic therapy

Abstract

Fibrotic diseases pose significant clinical challenges due to their broadness and complexity. Thus, a better understanding of fibrogenesis and the development of more effective treatments is imperative. Recent evidence suggests a significant antifibrotic potential of an endogenous glycoprotein, endostatin. While endostatin has been widely studied for its role as an anticancer adjuvant by inhibiting tumor angiogenesis, its possible implication in fibrosis remains largely unclear. Here, we review the role of endostatin in various cellular processes and highlight its antifibrotic activity. We hypothesize that endostatin conveys a homeostatic function in the process of fibrosis by regulating (a) TGF-β1 and its downstream signaling; (b) RhoA/ROCK pathway; (c) NF-κB signaling pathway; (d) expression of EGR-1; (e) PDGF/PDGFR pathway; (f) autophagy-related pathways; (g) pathways associated with cell proliferation and apoptosis. Finally, we propose a schematic model of the antifibrotic roles and mechanisms of endostatin; also, we outline future research directions of endostatin and aim to present a potential therapeutic approach for fibrosis.

Facile Preparation of Drug-Releasing Supramolecular Hydrogel for Preventing Postoperative Peritoneal Adhesion

“…They almost always occur after abdominal or pelvic surgery, leading to difficult complications such as chronic abdominal pain, intestinal obstruction, and female infertility. 70,71 Adhesion development is often accompanied by an increase in inflammation. Therefore, we established the classical adhesion model to evaluate the antiadhesion effects of the hydrogel as a barrier material.…”

“…Based on these results, we chose the widely adopted cecum-sidewall model to test the ability of the PVA/QUE hydrogel to prevent postoperative tissue adhesion. − Postoperative adhesions are a common clinical complication and a major concern for surgeons. They almost always occur after abdominal or pelvic surgery, leading to difficult complications such as chronic abdominal pain, intestinal obstruction, and female infertility. , Adhesion development is often accompanied by an increase in inflammation. Therefore, we established the classical adhesion model to evaluate the antiadhesion effects of the hydrogel as a barrier material.…”

c-KIT inhibitors reduce pathology and improve behavior in the Tg(SwDI) model of Alzheimer’s disease

“…Binding specificity of BK40143 and BK40197 revealed binding to major protein kinases involved in autophagy, including ULK3 ( Gonzalez-Rodriguez et al, 2022 ), mTOR ( Wang & Zhang, 2019 ), PDGFRs ( Zhang et al, 2021b ), PIKFYVE ( O’Connell & Vassilev, 2021 ), as well as c-KIT ( Lee et al, 2013 ). To establish that treatment with BK40143 and BK40197 induces autophagy, human SH-SY5Y neuroblastoma cells were transfected with an α-synuclein plasmid before being treated with rapamycin/chloroquine as a positive control, DMSO as a negative control, or an ascending dose (10, 1, or 100 μM) of either BK40143 or BK40197 for 8 h. Cells were then harvested and treated using the Abcam Autophagy Assay kit, which uses a cationic amphiphilic tracer to stain autophagic vacuoles, before analysis via flow cytometry.…”

Proteomic profile analysis of plasma and aqueous humor from glaucoma and non-glaucomatous patients

“…Interestingly, endostatin has been reported to promote expression and release of thrombospondin-1, implicated in outflow resistance & glaucoma [60][61][62] , in non-ocular endothelial cells 63 . Conversely, endostatin has also been posited to crosstalk with Rho/ROCK, TGFβ, NF-κB, PDGF, and autophagy pathways to yield anti-fibrotic effects 64 . SVEP1, another overexpressed secreted ECM protein in AH & a disease modifier allele for congenital glaucoma 65 , is known to be a binding partner for Tie1 and can thus regulate signaling outcomes in lymphatics and vasculature 66 .…”