Srivastava, R. | bioRxiv Science

bioRxiv2018

TCF7L2 Regulation of GATA6-dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia

Genetic variations in Wnt-coreceptor LRP6 and Wnt-regulated transcription factor TCF7L2 have been among the strongest genetic signals for type2 diabetes (T2DM) and coronary artery disease (CAD). Mice with a CAD-linked LRP6 mutation exhibit obstructive coronary artery disease characterized by reduced TCF7L2 expression and dedifferentiation of vascular smooth muscle cell (VSMC). While TCF7L2 maintains stemness and promotes proliferation in embryonic tissues and adult stem cells, its role and mechanisms of action in VSMC differentiation is not understood. Using multiple mouse models, we demonstrate here that TCF7L2 promotes differentiation and inhibits proliferation of VSMCs. TCF7L2 accomplishes these effects by stabilization of GATA6 and upregulation of SM-MHC and cell cycle inhibitors. Accordingly, TCF7L2 haploinsufficient mice exhibited increased susceptibility to, while mice overexpressing TCF7L2 were protected against injury-induced intimal hyperplasia compared to wildtype littermates. Consequently, the overexpression of TCF7L2 in LRP6 mutant mice rescued the injury induced intimal hyperplasia. These novel findings imply cell type-specific functional role of TCF7L2 and provide critical insight into poorly understood mechanisms underlying pathogenesis of intimal hyperplasia.

molecular biology↗

bioRxiv2018

FITC Conjugated Polycaprolactone-Glycol-Chitosan Nanoparticles Containing The Longwave Emitting Fluorophore IR 820 For In-Vitro Tracking Of Hyperthermia-Induced Cell Death

Cancer theranostic agent IR 820 loses its bioimaging ability once therapy is initiated. At the end of therapy, it becomes difficult to track the cancer cells. To address this, FITC conjugated Polycaprolactone glycol chitosan IR 820 nanoparticles (FITC-PCLGC-IR NPs) has been synthesized for in vitro tracking of hyperthemia induced cell death. Two approaches, namely ex situ and in situ have been pursued FITC conjugation to PCLGC-IR NPs. Further comparisons were made to FITC encapsulated PCLGC-IR NPs in terms of biocompatibility, cellular uptake, photothermal mediated cell death and imaging with respect to laser treatment. We have shown that an 808 nm diode laser treatment did not affect the imaging ability of these NPs whereas cancer. Time scanned fluorescence shows the excellent photostability of this formulation for a maximum of 5 min. The detailed studies of these approaches summarize that FITC conjugation to PCLGC-IR nanoparticles is an effective nano-theranostic solution for image-guided photothermal therapy.

bioengineering↗