John Garner

Thermogelling PLGA-PEG-PLGA from PolySciTech used in research of healing/scar-formation of cardiovascular tissue

Blog Post created by John Garner on Mar 15, 2019

Jing Li, 2019 cardiovascular polyscitech scar thermogel.jpg

The formation of scar tissue, or fibrosis, is a common response to injury and is part of the healing process of most tissues. Superficial scarring is benign however when it occurs in critical areas (such as cardiovascular tissue post balloon angioplasty) it can be lethal. Recently, researchers at The Ohio State University and University of Wisconsin used thermogelling PLGA-PEG-PLGA (AK012) from PolySciTech (www.polyscitech.com) to deliver centrinone-B (a PLK4 inhibitor) as part of modeling the effect that blocking PLK4 had on healing and scar formation. This research holds promise to aid in developing therapeutics to improve cardiovascular healing as part of treatment of atherosclerosis and hypertension. Read more: Jing Li, Go Urabe, Mengxue Zhang, Yitao Huang, Bowen Wang, Lynn Marcho, Hongtao Shen, K. Craig Kent, Lian-Wang Guo “A non-canonical role of polo-like kinase-4 in adventitial fibroblast cell type transition” bioRxiv (2019) 570267; doi: https://doi.org/10.1101/570267

 

“Abstract: Fibroblast-to-myofibroblast transition (FMT) is central to fibrosis. A divergent member of the polo-like kinase family, PLK4 is known for its canonical role in centriole duplication. Whether this mitotic factor regulates cell type transitions was underexplored. Here we investigated PLK4’s activation and expression and regulations thereof in platelet-derived growth factor (PDGF)- induced FMT of rat aortic adventitial fibroblasts. PLK4 inhibition (with centrinone-B or siRNA) diminished not only PDGF AA-induced proliferation/migration, but also smooth muscle a-actin and its transcription factor serum response factor’s activity. While PDGFR inhibition abrogated AA-stimulated PLK4 activation (phosphorylation) and mRNA/protein expression, inhibition of p38 downstream of PDGFR had a similar effect. Further, the transcription of PLK4 (and PDGFRa) was blocked by pan-inhibition of the bromo/extraterminal-domains chromatin-bookmark readers (BRD2, BRD3, BRD4), an effect herein determined via siRNAs as mainly mediated by BRD4. In vivo, periadventitial administration of centrinone-B reduced collagen content and thickness of the adventitia in a rat model of carotid artery injury. Thus, we identified a non-canonical role for PLK4 in FMT and its regulation by a BRD4/PDGFRa-dominated pathway. This study implicates a potential PLK4-targeted antifibrotic intervention. Keywords: PLK4, PDGF receptor-a, BRD4, fibroblast-to-myofibroblast transition, fibrosis”

 

- Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

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