Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the rat lung, primary saccules are transformed into alveoli from postnatal Days 4 to 13, after which time there is a 20% reduction in the number of lung fibroblasts as the interstitial volume of the alveolar walls decreases. Our objective was to determine whether apoptosis is a factor in the observed decrease in the number of interstitial lung fibroblasts beyond Day 13. We used both histologic and flow cytometric assays to detect in lung fibroblasts the DNA fragmentation and condensation that are characteristic of apoptosis. In addition, we evaluated levels of bcl-2 and BAX messenger RNAs (mRNAs) using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Apoptotic cells were quantitated in glycol methacrylate-embedded sections of neonatal rat lungs using the terminal transferase dUTP-digoxygenin nick end-labeling (TUNEL) method. Although TUNEL-positive interstitial cells were observed in the lungs of rats ranging in age from 10 to 16 d, a dramatic increase in apoptotic cells was seen on Day 17. Although diminished in number, TUNEL-positive cells were still present on Day 28. Hoechst-stained apoptotic bodies were observed in isolated lung cells that were vimentin-positive and factor VIII-negative, which identified the apoptotic cells as fibroblasts as opposed to endothelial cells. Flow cytometric analysis of freshly isolated lung fibroblasts stained with Hoechst 33342 indicated a 24% increase in chromatin condensation in cells from 17-d versus 16-d rats. DNA fragmentation was also quantitated by flow cytometry in freshly isolated fibroblasts labeled with BODIPY-conjugated dUTP in the presence of terminal deoxynucleotidyl transferase. The percentage of lung fibroblasts containing fragmented DNA was 51.4 +/- 13.4 in 17-d, 36.9 +/- 8.6 in 18-d, and 13.8 +/- 5.4 in 19-d rat pups. Finally, evaluation by RT-PCR indicated that on postnatal Day 17, mRNA for bcl-2, which inhibits apoptosis, was decreased to 73.5 +/- 11.4% (P < 0.001) of Day 5 controls; whereas mRNA for BAX, which enhances apoptosis, was increased to 243.0 +/- 102.0% (P < 0.001) of Day 5 values. These results demonstrate that rat lung fibroblasts undergo apoptosis after the completion of alveolarization, and suggest that this decrease in fibroblast number plays an important role in the thinning and remodeling of the alveolar walls of the lung.
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PMID:Lung fibroblasts undergo apoptosis following alveolarization. 992 13

Acute coronary occlusion results in ischemia-mediated death of cardiomyocytes. In the days and weeks following myocardial infarction (MI), left ventricular remodeling occurs that is characterized by persistent cardiomyocyte apoptosis, thinning and fibrosis at the site of infarction, ventricular chamber dilatation, and growth of remaining viable cardiomyocytes. The p38 mitogen-activated protein kinase (MAPK) signaling cascade has been implicated in the remodeling process. In this work, mice with cardiac-specific expression of a dominant negative mutant form of p38 MAPK (DN-p38alpha) were subjected to MI by occlusion of the left coronary artery. Acute ischemia area was determined by transthoracic echocardiography 2 h after MI surgery, and was found to be nearly identical in DN-p38 mice and their wild-type littermates. Seven days after MI, mice were subjected to repeat echocardiography and histological examination of infarct size. DN-p38 mice had markedly reduced infarct size and increased ventricular systolic function 7 days after MI when compared to wild-type littermates. In addition, DN-p38 mice had less cardiomyocyte apoptosis than wild-type mice in the infarct border zone. Recently, it was discovered that Bcl-X(L) deamidation occurs in vivo, and this results in Bcl-X(L) degradation that sensitizes cells to apoptosis by enhancing BAX activity. Bcl-X(L) deamidation was found to occur in the cardiac tissue of wild-type mice after MI, but was reduced in DN-p38 mice. These results establish that p38 MAPK activity is required for pathological remodeling after MI and suggest that p38 MAPK may promote cardiomyocyte apoptosis through Bcl-X(L) deamidation.
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PMID:Role of p38alpha MAPK in cardiac apoptosis and remodeling after myocardial infarction. 1580 38