Prolyl-3-hydroxylase 4 (P3H4), a novel player in collagen synthesis and secretion in lung fibroblasts

Onursal, Ceylan; Knüppel, Larissa; Merl-Pham, Juliane; Lietman, Caressa; Hatz, Rudolf; Behr, Jürgen; Unger, Kristian; Heß, Julia; Hauck, Stefanie M.; Lee, Brendan; Staab-Weijnitz, Claudia A.

doi:10.1183/13993003.congress-2021.pa3283

Cited by 2 publications

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“…Prolyl 3-hydroxylase family member 4 (P3H4/LEPREL4/SC65) is a member of the collagen Leprecan family proteins, which are critical components of endoplasmic reticulum-resident collagen [ 20 , 21 ]. P3H4 is an autoantigen associated with several types of human diseases, including cancers [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Efficient Delivery of P3H4 siRNA and Chlorin e6 by cRGDfK-Installed Polyarginine Nanoparticles for Tumor-Targeting Therapy of Bladder Cancer

et al. 2022

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Purpose: Prolyl 3-hydroxylase family member 4 (P3H4) is a potent prognostic oncogene in bladder cancer (BC), and the inhibition of P3H4 suppresses BC tumor growth. This study aimed to evaluate the efficiency of P3H4 inhibition for BC tumor therapy via tumor-targeting nanoparticles. Methods and results: A linear polyarginine peptide (R9) was synthesized, azide-modified, and then assembled with cyclic pentapeptide cRGDfK. Chlorin e6 (ce6)-conjugated CH3-R9-RGD nanoparticles were prepared for the delivery of siP3H4 into T24 cells in vitro and BC tumors in vivo. Dynamic light scattering analysis identified that the optimum CH3-R9-RGD@siP3H4 molar ratio was 30/1. CH3-R9-RGD@ce6/siP3H4 nanocomposites decreased P3H4 expression and cell proliferation and promoted reactive oxygen species production, apoptosis, and calreticulin exposure in T24 cells in vitro. In vivo experiments showed that CH3-R9-RGD@ce6/siP3H4 nanocomposites caused pathological changes, suppressed BC tumor growth, promoted caspase 3 expression, and enhanced calreticulin exposure in tumor cells. Conclusions: The tumor-targeting CH3-R9-RGD nanocomposites encapsulating siP3H4 and ce6 might be an alternative therapeutic strategy or intravesical instillation chemotherapy for BC.

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