Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0206061 (interstitial pneumonia)
 6,105 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice were injected with 400 mg. per kg. of butylated hydroxytoluene (BHT) and exposed to an atmosphere of 70 per cent oxygen for 6 days. Control groups were animals treated with BHT alone or injected with vehicle and kept for 6 days in either O2 or air. Animals were killed at various time intervals after BHT treatment, and the lung changes were evaluated with biochemical and morphologic techniques. In animals exposed to BHT + O2, there was initially a diffuse interstitial pneumonitis, increased levels of interstitial collagen, and a decreased ratio of type III to type I collagen. With time the inflammatory component subsided, and degenerative changes primarily consisting of dilation of terminal airways and of alveoli became apparent. Elevated levels of lung hydroxyproline persisted until the termination of the study at 1 year, although ratios of type III to type I collagen returned to normal. In animals treated with BHT alone, collagen accumulation and morphologic changes were similar, although much less severe. It is concluded that potentiation of acute lung injury by oxygen produces long-lasting morphologic and biochemical alterations in lung parenchyma.
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PMID:Long-term morphologic and biochemical features of experimentally induced lung fibrosis in the mouse. 707 57

Osteopontin is a multifunctional matricellular protein abundantly expressed during inflammation and repair. Osteopontin deficiency is associated with abnormal wound repair characterized by aberrant collagen fibrillogenesis in the heart and skin. Recent gene microarray studies found that osteopontin is abundantly expressed in both human and mouse lung fibrosis. Macrophages and T cells are known to be major sources of osteopontin. During lung fibrosis, however, osteopontin expression continues to increase when inflammation has receded, suggesting alternative sources of ostepontin during this response. In this study, we demonstrate immunoreactivity for osteopontin in lung epithelial and inflammatory cells in human usual interstitial pneumonitis and murine bleomycin-induced lung fibrosis. After treatment with bleomycin, osteopontin-null mice develop lung fibrosis characterized by dilated distal air spaces and reduced type I collagen expression compared with wild-type controls. There is also a significant decrease in levels of active transforming growth factor-beta(1) and matrix metalloproteinase-2 in osteopontin null mice. Type III collagen expression and total collagenase activity are similar in both groups. These results demonstrate that osteopontin expression is associated with important fibrogenic signals in the lung and that the epithelium may be an important source of osteopontin during lung fibrosis.
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PMID:Altered bleomycin-induced lung fibrosis in osteopontin-deficient mice. 1497 30

It has been shown in many investigations that the abnormally increasing production and deposition of collagen is one of the important mechanisms of pathological scars and other fibrotic diseases [Wang Z, Inokuchi T, Nemoto TK, Uehara M, Baba TT. Antisense oligonucleotide against collagen-specific molecular chaperone 47-kDa heat shock protein suppresses scar formation in rat wounds. Plast Reconstr Surg 2003 May; 111(6):1980-7; Obayashi K, Akamatsu H, Okano Y, Matsunage K, Masaki H. Exogenous nitric oxide enhances the synthesis of type I collagen and heat shock protein 47 by normal human dermal fibroblasts. J Dermatol Sci 2006 Feb; 41(2): 121-6 [e pub. 2005 Sep 19]; Kakugawa T, Mukae H, Hayashi T, Ishii H, Nakayama S, Sakamoto N, et-al. Expression of HSP47 in usual interstitial pneumonia and nonspecific interstitial pneumonia. Respir Res 2005 Jun;14(6): 57; Razzaque MS, Taguchi T. The possible role of colligin/HSP47, a collagen-binding protein, in the pathogenesis of human and experimental fibrotic diseases. Histol Histopathol 1999 Oct; 14(4): 1199-1212; Sharp PA. RNA interference - 2001. Genes Dev 2001 Mar 1; 15(5): 485-90; Ohashi S, Abe H, Takahashi T, Yamamoto Y, Takeuchi M, Arai H, et-al. Advanced glycation end products increase collagen-specific chaperone protein in mouse diabetic nephropathy. J Biol Chem 2004 May 7; 279(19): 19816-23 [epub 2004 Mar 5]]. RNA interference is the process that double-stranded RNA induces the homology-dependent degradation of cognate mRNA mediated by 21-23 nucleotide short interfering RNA (siRNA). In this study, we investigated the effect of HSP47-specific siRNA on the fibroblast cells, and then constructed adenovirus containing siRNA against HSP47 to inhibit the formation of scar in animal model. In this pilot study, HSP47 was targeted by this vector. Our results showed that the HSP47-specific siRNA could inhibit the expression of HSP47 at the level of mRNA and protein. Furthermore, adenovirus-mediated transfer of siRNA against HSP47 could inhibit the expression of type I collagen and the formation of scar tissue in animal model. It is likely that the inhibition of HSP47 by RNA interference (RNAi) could be developed as a powerful approach to prevent the scar formation.
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PMID:Adenovirus-mediated RNA interference against collagen-specific molecular chaperone 47-KDa heat shock protein suppresses scar formation on mouse wounds. 1809 50

Acute respiratory distress syndrome is a severe disease, the treatment and pathophysiology of which are not completely established. The pathology of acute respiratory distress syndrome involves diffuse alveolar damage, which comprises severe alveolar epithelial cell damage, hyaline membrane formation, and festinate myofibroblast proliferation and fibrosis in the intra-alveolar spaces. We performed a clinicopathologic investigation of 26 autopsy cases of diffuse alveolar damage. Three cases of them were diagnosed as acute interstitial pneumonia that is idiopathic illness and resembles pathologically organizing diffuse alveolar damage. Immunohistochemical staining for types I and IV collagen, alpha-smooth muscle actin, and Ki-67 was carried out, and the sites of myofibroblast proliferation and type I collagen production were examined. All diffuse alveolar damage cases in the proliferative phase showed intra-alveolar myofibroblast proliferation. When diffuse alveolar damage was diagnosed pathologically as being due to severe infection, all 7 patients showed multiple organ dysfunction syndrome, whereas only 2 of 7 patients showed interstitial myofibroblast proliferation. When diffuse alveolar damage was attributed to tumor treatment with chemotherapy or to drug toxicity, 3 of 16 patients showed multiple organ dysfunction syndrome; 15 of 16 showed interstitial myofibroblast proliferation, 3 of 3 acute interstitial pneumonia patients did not show multiple organ dysfunction syndrome; and 3 of 3 acute interstitial pneumonia showed marked interstitial myofibroblast proliferation. These results suggest that the pathophysiologic mechanism of diffuse alveolar damage caused by severe infection is one of systemic circulation disturbance, although the mechanism underlying diffuse alveolar damage due to tumor with chemotherapy or drug toxicity appears to involve interstitial pneumonia-like lesions that are similar to acute interstitial pneumonia.
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PMID:Two forms of diffuse alveolar damage in the lungs of patients with acute respiratory distress syndrome. 1964 54

Idiopathic pulmonary fibrosis is a chronic, progressive, fibrosing interstitial pneumonia of unknown cause resulting in dyspnea and functional decline until death. There are currently no effective noninvasive tools to monitor disease progression and response to treatment. The objective of the present study was to determine whether molecular magnetic resonance imaging of the lung using a probe targeted to type I collagen could provide a direct, noninvasive method for assessment of pulmonary fibrosis in a mouse model. Pulmonary fibrosis was generated in mice by transtracheal instillation of bleomycin (BM). Six cohorts were imaged before and immediately after intravenous administration of molecular imaging probe: (1) BM plus collagen-targeted probe, EP-3533; (2) sham plus EP-3533; (3) BM plus nonbinding control probe, EP-3612; (4) sham plus EP-3612; (5) BM plus EP-3533 imaged early; and (6) BM plus EP-3533 imaged late. Signal-to-noise ratio (SNR) enhancement was quantified in the lungs and muscle. Lung tissue was subjected to pathologic scoring of fibrosis and analyzed for gadolinium and hydroxyproline. BM-treated mice had 35% higher lung collagen than sham mice (P < 0.0001). The SNR increase in the lungs of fibrotic mice after EP-3533 administration was twofold higher than in sham animals and twofold higher than in fibrotic or sham mice that received control probe, EP-3612 (P < 0.0001). The SNR increase in muscle was similar for all cohorts. For EP-3533, we observed a strong, positive, linear correlation between lung SNR increase and hydroxyproline levels (r = 0.72). Collagen-targeted probe EP-3533-enhanced magnetic resonance imaging specifically detects pulmonary fibrosis in a mouse model of disease.
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PMID:Molecular magnetic resonance imaging of pulmonary fibrosis in mice. 2392 43