Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lens epithelial cells undergo epithelial-mesenchymal transition (EMT) after injury as in cataract extraction, leading to fibrosis of the lens capsule. Fibrosis of the anterior capsule can be modeled in the mouse by capsular injury in the lens, which results in EMT of the lens epithelium and subsequent deposition of extracellular matrix without contamination of other cell types from outside the lens. We have previously shown that signaling via Smad3, a key signal-transducing element downstream of transforming growth factor (TGF)-beta and activin receptors, is activated in lens epithelial cells by 12 hours after injury and that this Smad3 activation is blocked by administration of a TGF-beta 2-neutralizing antibody in mice. We now show that EMT of primary lens epithelial cells in vitro depends on TGF-beta expression and that injury-induced EMT in vivo depends, more specifically, on signaling via Smad3. Loss of Smad3 in mice blocks both morphological changes of lens epithelium to a mesenchymal phenotype and expression of the EMT markers snail, alpha-smooth muscle actin, lumican, and type I collagen in response to injury in vivo or to exposure to exogenous TGF-beta in organ culture. The results suggest that blocking the Smad3 pathway might be beneficial in inhibiting capsular fibrosis after injury and/or surgery.
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PMID:Smad3 signaling is required for epithelial-mesenchymal transition of lens epithelium after injury. 1474 69

Bone morphogenetic proteins (BMPs) and activins are multifunctional growth factors, which also affect wound healing and tissue fibrosis. To determine their putative role in conjunctival wound healing and scarring, we investigated the expression of various BMPs, BMP receptors, and activins in normal and scarred human conjunctival tissue and in cultured human Tenon's capsule fibroblasts on the mRNA and protein level. Messenger RNA expression of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, the BMP receptors type I (BMPR-IA, BMPR-IB) and II (BMPR-II), and of activin A and B was investigated by semi-quantitative RT-PCR in normal conjunctival specimens and in scarred filtering blebs as well as in cultured Tenon's capsule fibroblasts obtained from patients with primary open-angle glaucoma (POAG), pseudoexfoliation (PEX) glaucoma and cataract. Immunohistochemistry was used to study the protein expression of BMP-2, BMP-4, BMP-6, BMP-7, and activin A in normal and scarred conjunctival tissue as well as in cultured Tenon's capsule fibroblasts. BMP-2, BMP-3, BMP-4, BMP-6, BMP-7, all BMP receptors, and activin A were expressed on the mRNA and protein level in conjunctival biopsies without showing any differences between groups of patients. The mRNA and protein expression of both BMP-6 and activin A was found to be significantly increased in scar tissue compared with normal conjunctiva and could be immunolocalized to epithelial cells, vascular endothelia, stromal fibroblasts, and macrophage-like cells. However, no significant increase in receptor gene expression was observed in scar tissue. With the exception of BMP-7, all growth factors and receptors were also expressed in cultured Tenon's fibroblasts without showing any differences between cultures derived from normal and scarred conjunctival specimens. These findings suggest various BMPs and activin A as components of the conjunctival cytokine meshwork regulating tissue homeostasis and wound healing and provide evidence that alterations in the expression of BMP-6 and activin A, in particular, are associated with conjunctival scarring. Modulation of BMP/activin activities may, therefore, be explored as new approaches for managing postoperative conjunctival scarring responses in glaucoma patients.
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PMID:Expression of bone morphogenetic proteins (BMPs), their receptors, and activins in normal and scarred conjunctiva: role of BMP-6 and activin-A in conjunctival scarring? 1687 18