The American Journal of Pathology

Journal Information
ISSN / EISSN : 0002-9440 / 1525-2191
Current Publisher: Elsevier BV (10.1016)
Former Publisher:
Total articles ≅ 9,468
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The American Journal of Pathology, Volume 191, pp 967-967; doi:10.1016/j.ajpath.2021.04.002

Gun-Dong Kim, Hang Pong Ng, ,
The American Journal of Pathology, Volume 191, pp 1118-1134; doi:10.1016/j.ajpath.2021.03.008

The publisher has not yet granted permission to display this abstract.
, Saori Nishikawa, Junichi Hosoi, Satoshi Amano
The American Journal of Pathology, Volume 191, pp 1010-1019; doi:10.1016/j.ajpath.2021.03.007

Abstract:
Hyaluronan (HA) is the major glycosaminoglycan in the extracellular matrix of most mammalian tissues, including the epidermis. It is synthesized in epidermis, and mainly metabolized after transfer to the liver via lymphatic vessels in the dermis following its passage through the basement membrane (BM) at the dermal-epidermal junction. The aim of the present study was to investigate the influence of BM integrity on the level of HA in the epidermis. Epidermal HA content was decreased in sun-exposed skin of older subjects, whose BM structure was impaired, compared with sun-exposed young skin and sun-protected skin, in which BM integrity was well maintained. In an organotypic culture model of sun-exposed facial skin, epidermal HA was increased in the presence of inhibitors of BM-degrading matrix metalloproteinases and heparanase. In a skin equivalent model treated with these inhibitors, HA content was increased in the epidermis, but decreased in conditioned medium. These findings suggest that the BM at the dermal-epidermal junction plays an important role in maintaining epidermal HA levels.
Padmashree Rao, Xi Qiao, Winston Hua, , Mariah Tahan, Titi Chen, Hong Yu, Xiaojun Ren, Qi Cao, Yiping Wang, et al.
The American Journal of Pathology, Volume 191, pp 993-1009; doi:10.1016/j.ajpath.2021.03.005

Abstract:
Fibrosis is characterized by progressively excessive deposition of matrix components and may lead to organ failure. Transforming growth factor-β (TGF-β) is a key cytokine involved in tissue repair and fibrosis. TGF-β′s profibrotic signaling pathways converge at activation of β-catenin. β-Catenin is an important transcription cofactor whose function depends on its binding partner. Promoting β-catenin binding to forkhead box protein O (Foxo) via inhibition of its binding to T-cell factor (TCF) reduces kidney fibrosis in experimental murine models. Herein, we investigated whether β-catenin/Foxo diverts TGF-β signaling from profibrotic to physiological epithelial healing. In an in vitro model of wound healing (scratch assay), and in an in vivo model of kidney injury, unilateral renal ischemia reperfusion, TGF-β treatment in combination with either ICG-001 or iCRT3 (β-catenin/TCF inhibitors) increased β-catenin/Foxo interaction, increased scratch closure by increased cell proliferation and migration, reduced the TGF-β–induced mesenchymal differentiation, and healed the ischemia reperfusion injury with less fibrosis. In addition, administration of ICG-001 or iCRT3 reduced the contractile activity induced by TGF-β in C1.1 cells. Together, our results indicate that redirection of β-catenin binding from TCF to Foxo promotes β-catenin/Foxo–mediated epithelial repair. Targeting β-catenin/Foxo may rebuild normal structure of injured kidney.
Monica Sanchez-Ruiz, Ana-Maria Iorgu, Florian Küster, Martin Hellmich, Anna Brunn, Martina Deckert
The American Journal of Pathology, Volume 191, pp 1064-1076; doi:10.1016/j.ajpath.2021.02.021

The publisher has not yet granted permission to display this abstract.
Erratum
The American Journal of Pathology, Volume 191, pp 1151-1152; doi:10.1016/j.ajpath.2021.04.001

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Erratum
The American Journal of Pathology, Volume 191; doi:10.1016/j.ajpath.2021.03.010

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Tobias Furlan, Alexander Kirchmair, Natalie Sampson, Martin Puhr, Martina Gruber, Zlatko Trajanoski, Frédéric R. Santer, Walther Parson, Florian Handle,
The American Journal of Pathology, Volume 191, pp 1094-1107; doi:10.1016/j.ajpath.2021.02.017

Abstract:
Patients with advanced prostate cancer are frequently treated with the antiandrogen enzalutamide. However, resistance eventually develops in virtually all patients, and various mechanisms have been associated with this process. The histone acetyltransferases EP300 and CREBBP are involved in regulation of cellular events in advanced prostate cancer. This study investigated the role of EP300/CREBBP inhibitors in enzalutamide-resistant prostate cancer. EP300/CREBBP inhibitors led to the same inhibition of androgen receptor activity in enzalutamide-resistant and -sensitive cells. However, enzalutamide-resistant cells were more sensitive to these inhibitors in viability assays. As indicated by the RNA-sequencing–based pathway analysis, genes related to the ribosome and MYC activity were significantly altered upon EP300/CREBBP inhibitor treatment. EP300/CREBBP inhibitors led to the down-regulation of ribosomal proteins RPL36 and RPL29. High-level ribosomal proteins amplifications and MYC amplifications were observed in castration-resistant prostate cancer samples of the publicly available Stand Up to Cancer data set. An inhibitor of RNA polymerase I–mediated transcription was used to evaluate the functional implications of these findings. The enzalutamide-resistant cell lines were more sensitive to this treatment. In addition, the migration rate of enzalutamide-resistant cells was strongly inhibited by this treatment. Taken together, the current data show that EP300/CREBBP inhibitors affect the MYC/ribosomal protein axis in enzalutamide-resistant cells and may have promising therapeutic implications.
, Randall J. Olsen, Paul A. Christensen, Sishir Subedi, Robert Olson, James J. Davis, , Prasanti Yerramilli, Layne Pruitt, Kristina Reppond, et al.
The American Journal of Pathology, Volume 191, pp 983-992; doi:10.1016/j.ajpath.2021.03.004

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Shanshan Qin, Dan Predescu, Brandon Carman, Priyam Patel, Jiwang Chen, Miran Kim, Tim Lahm, Mark Geraci, Sanda A. Predescu
The American Journal of Pathology, Volume 191, pp 1135-1150; doi:10.1016/j.ajpath.2021.03.009

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