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Transforming Growth Factor: β3 Regulates Cell Metabolism in Corneal Keratocytes and Fibroblasts

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Studies on the Cornea and Lens

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Abstract

Corneal keratocytes (HCKs) are specialized cells that reside in the corneal stroma, the largest layer of the human cornea. HCKs play a major role in corneal transparency and orchestrate corneal wound healing upon injury. Following an injury to the cornea HCKs adjacent to the wound undergo apoptosis and HCKs outside the wound area are activated, and they assume the role of remodeling the damaged stroma. Once activated the cells are termed fibroblasts (HCF). One of the key factors of this activation is thought to be transforming growth factor-beta (TGF-β). Five TGF-β (-β1,-β2,-β3,-β4, and -β5) have been identified and three (-β1,-β2, and -β3) are found in humans. We have recently identified TGF-β3 as a growth factor that can reduce or rescue corneal fibrosis in vitro. In this chapter, we present evidence that TGF-β3 plays a major role in regulating the metabolism of both HCKs and HCFs in vitro. We investigated both a conventional monolayer 2D system and a 3D self-assembled extracellular matrix (ECM) model. We targeted a total of 256 endogenous water-soluble metabolites by LC-MS/MS of which more than 60 were significantly regulated between different groups. These findings are expected to help achieve a better understanding of the specific and redundant functions of these metabolites.

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Abbreviations

ECM:

Extracellular matrix

GNG:

Glucogenesis

HCF:

Human corneal fibroblasts

HCK:

Human corneal keratocytes

TCA:

Tricarboxylic acid cycle

TGF-β:

Transforming growth factor-beta

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Acknowledgments

This work was supported by National Institutes of Health Grant EY023568 (D.K) and EY020886 (DK and JDZ)

Author information

Authors and Affiliations

  1. Department of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Boulevard, DMEI PA-409, Oklahoma City, OK, 73104, USA

    D. Karamichos

  2. Division of Signal Transduction and Mass Spectrometry Core, Beth Israel Deaconess Medical Center and the Department of Medicine, Harvard Medical School, Boston, MA, USA

    J. M. Asara

  3. Schepens Eye Research Institute/Massachusetts Eye and Ear and the Department of Ophthalmology, Harvard Medical School, Boston, MA, USA

    J. D. Zieske

Authors
  1. D. Karamichos
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  2. J. M. Asara
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  3. J. D. Zieske
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Corresponding author

Correspondence to D. Karamichos .

Editor information

Editors and Affiliations

  1. Innovative Vision Products Inc., Moscow, Russia, Innovative Vision Products, Inc.,, County of New Castle, Delaware, USA

    Mark A. Babizhayev

  2. Department of Ophthalmology and Visual Sciences, Truhlsen Eye Institute, College of Medicine, University of Nebraska Medical Center; Key Laboratory of Protein Chemistry and Developmental Biology of Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China, Omaha, Nebraska, USA

    David Wan-Cheng Li

  3. Department of Pharmaceutical Sciences and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Anne Kasus-Jacobi

  4. Department of Ophthalmology, University of Pristina, Faculty of Medicine, Kosovska Mitrovica, Serbia

    Lepša Žorić

  5. Ophthalmology, Miguel Hernandez University, Alicante, Spain

    Jorge L. Alió

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Karamichos, D., Asara, J.M., Zieske, J.D. (2015). Transforming Growth Factor: β3 Regulates Cell Metabolism in Corneal Keratocytes and Fibroblasts. In: Babizhayev, M., Li, DC., Kasus-Jacobi, A., Žorić, L., Alió, J. (eds) Studies on the Cornea and Lens. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1935-2_5

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