Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 183, Issue 1, Pages 247-256Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2013.04.001
Keywords
-
Categories
Funding
- [NIHEY05129]
Ask authors/readers for more resources
Decorin, a small Leucine-rich proteoglycan (SLRP), is involved in the pathophysiology of human congenital stromal corneal dystrophy (CSCD). This disease is characterized by corneal opacities and vision impairment. In reported cases, the human gene encoding decorin contains point mutations in exon 10, generating a truncated form of decotin lacking the C-terminal 33 amino acid residues. We have previously described a transgenic mouse model carrying a similar mutation in the decorin gene that leads to an ocular phenotype characterized by corneal opacities identical to CSCD in humans. We have also identified abnormal synthesis and secretion of various SLRPs in mutant mouse corneas. In the present study, we found that mutant C-terminal truncated decorin was retained in the cytoplasm of mouse keratocytes in vivo and of transfected human embryonic kidney cells. This resulted in endoplasmic reticulum stress and an unfolded protein response. Thus, we propose a novel cell-based mechanism underlying CSCD in which a truncated SLRP protein core is retained intracellularly, its accumulation triggering endoplasmic reticulum stress that results in abnormal SLRP synthesis and secretion, which ultimately affects stromal structure and corneal transparency.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available