Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell-mediated contraction of tissues containing fibrillar collagens can lead to organ compromise and loss of function. The same process that is biologically advantageous during the contraction phase of wound healing can be subverted in diseases such as hepatic cirrhosis, pulmonary fibrosis, and scleroderma, although the cellular and molecular mechanism of matrix tissue contraction is difficult to study in such chronic diseases. However, certain human eye diseases that result in tractional detachment of the retina and loss of vision are characterized by acute cell-mediated contraction of collagenous tissue in the vitreous cavity. In this study, we demonstrate that human cells can contract vitreous, a complex biological gel containing type II collagen, in vitro. This cell-mediated contraction can be blocked by antibodies and peptides that antagonize the function of alpha 2 beta 1 integrin, and the potential for contraction can be conferred upon noncontracting cells by stable transfection of cells with alpha 2 cDNA. We also show that this contractile process, if focally resisted, can result in remodeling vitreous from a gel to a structure that resembles a planar membrane, and that substantial isometric forces can be measured across this tissue. We propose that in diseases such as proliferative diabetic retinopathy and proliferative vitreoretinopathy, alpha 2 beta 1 integrin-mediated contraction of the vitreous and tension at the site of vitreoretinal attachments contribute to the terminal event of tractional retinal detachment. By extension, we propose that alpha 2 beta 1 integrin is a centrally important molecule in human diseases characterized by remodeling and contraction of collagenous tissue (i.e., fibrocontractive diseases).
 ...
PMID:A potential pathophysiologic role for alpha 2 beta 1 integrin in human eye diseases involving vitreoretinal traction. 822 12

Fibrosis in ocular tissues causes severe visual deterioration and blindness in patients with glaucoma, cataract, age related macular degeneration (AMD) and diabetic retinopathy (DR). Currently available anti-fibrotic agents exhibit undesirous cytotoxic effects and thus prove ineffective to treat post-surgical fibrosis. Accordingly, there is a need to develop efficient and novel anti-fibrotic agents. Adiponectin (APN), an adipokine from adipocytes is increased in the aqueous and vitreous humor of the patients with micro-angiopathy and chronic inflammation. Furthermore, it is reported to be elevated in the subretinal fluid, vitreous and epiretinal membrane of patients with AMD, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR) respectively. Since APN has anti-angiogenic activity and reduces VEGF levels, we hypothesize that APN might regulate the angio-fibrotic switch and drive the formation of fibrovascular membrane at advanced stages of AMD, PVR and PDR. Intriguingly, APN is shown to inhibit liver, cardiac and pulmonary fibrosis, yet it accelerates renal fibrosis. Therefore, the factors such as tissue and cell type, disease specific pathological milieu and the choice of APN receptor interaction could determine the pro- or anti-fibrotic nature of APN. We speculate that APN could play a profibrotic role in the posterior segment of the eye.
 ...
PMID:Adiponectin: A potential candidate for treating fibrosis in posterior segment of the eye. 3069 4