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Cathepsin B is up-regulated and mediates extracellular matrix degradation in trabecular meshwork cells following phagocytic challenge.

Publication ,  Journal Article
Porter, K; Lin, Y; Liton, PB
Published in: PloS one
January 2013

Cells in the trabecular meshwork (TM), a tissue responsible for draining aqueous humor out of the eye, are known to be highly phagocytic. Phagocytic activity in TM cells is thought to play an important role in outflow pathway physiology. However, the molecular mechanisms triggered by phagocytosis in TM cells are unknown. Here we investigated the effects of chronic phagocytic stress on lysosomal function using different phagocytic ligands (E. coli, carboxylated beads, collagen I-coated beads, and pigment). Lysotracker red co-localization and electron micrographs showed the maturation of E. coli- and collagen I-coated beads-containing phagosomes into phagolysosomes. Maturation of phagosomes into phagolysosomes was not observed with carboxylated beads or pigment particles. In addition, phagocytosis of E. coli and collagen I-coated beads led to increased lysosomal mass, and the specific up-regulation and activity of cathepsin B (CTSB). Higher levels of membrane-bound and secreted CTSB were also detected. Moreover, in vivo zymography showed the intralysosomal degradation of ECM components associated with active CTSB, as well as an overall increased gelatinolytic activity in phagocytically challenged TM cells. This increased gelatinolytic activity with phagocytosis was partially blocked with an intracellular CTSB inhibitor. Altogether, these results suggest a potential role of phagocytosis in outflow pathway tissue homeostasis through the up-regulation and/or proteolytic activation of extracellular matrix remodeling genes.

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Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2013

Volume

8

Issue

7

Start / End Page

e68668

Related Subject Headings

  • Trabecular Meshwork
  • Swine
  • Proteolysis
  • Protein Transport
  • Phagosomes
  • Phagocytosis
  • Lysosomes
  • General Science & Technology
  • Gene Expression Regulation
  • Gelatin
 

Citation

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Porter, K., Lin, Y., & Liton, P. B. (2013). Cathepsin B is up-regulated and mediates extracellular matrix degradation in trabecular meshwork cells following phagocytic challenge. PloS One, 8(7), e68668. https://doi.org/10.1371/journal.pone.0068668
Porter, Kristine, Yizhi Lin, and Paloma B. Liton. “Cathepsin B is up-regulated and mediates extracellular matrix degradation in trabecular meshwork cells following phagocytic challenge.PloS One 8, no. 7 (January 2013): e68668. https://doi.org/10.1371/journal.pone.0068668.
Porter, Kristine, et al. “Cathepsin B is up-regulated and mediates extracellular matrix degradation in trabecular meshwork cells following phagocytic challenge.PloS One, vol. 8, no. 7, Jan. 2013, p. e68668. Epmc, doi:10.1371/journal.pone.0068668.

Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2013

Volume

8

Issue

7

Start / End Page

e68668

Related Subject Headings

  • Trabecular Meshwork
  • Swine
  • Proteolysis
  • Protein Transport
  • Phagosomes
  • Phagocytosis
  • Lysosomes
  • General Science & Technology
  • Gene Expression Regulation
  • Gelatin