Biomedical subjects

Kei Horiguchi

Publications and source records attributed to Kei Horiguchi.

3 recordsLinked to original sources

PubMed2005

Microarray-based gene expression profiling of retransplanted rat cardiac allografts that develop cardiac allograft vasculopathy.

We studied the expression of 9,906 genes in retransplanted rat cardiac allografts that developed cardiac allograft vasculopathy (CAV) with the use of DNA microarray and real-time reverse transcriptase-polymerase chain reaction. Although only a slight difference in the timing of the retransplantation induced the later development of CAV, 1,067 genes were differentially expressed in the allografts 1 day after retransplantation. Thus, the development of CAV was determined by a robust difference in gene expression soon after retransplantation, controlled by a slight difference in retransplantation timing. In contrast, only 26 genes showed significant upregulation in the later phase of CAV development, and the time-course of the induction of 16 genes was associated with CAV progression. Of these genes, 8 were induced in 2 different aortic allograft combinations, and the time-course of the induction was correlated with the development of transplant vasculopathy. Microarray-based gene expression profiling has the potential to elucidate the mechanism of experimental chronic cardiac allograft rejection.

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PubMed2003

Antibody deposition in rat heart which develops transplant vasculopathy in (donor x recipient) F1 environment.

PURPOSE: We studied the gene expression in rat cardiac allografts retransplanted into (donor x recipient) F1 animals to identify unknown or unexpected genes whose expression might contribute to the progression of transplant vasculopathy. METHODS: Gene expression was first studied using a mRNA differential display, then it was further investigated using quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. RESULTS: We found that the rat immunoglobulin kappa chain gene was preferentially induced in retransplanted cardiac allografts in which transplant vasculopathy was developing. The diseased vessels in the same allografts were heavily infiltrated with CD45R-positive B cells. The expression of two genes related to B-cell responses, B-lymphocyte chemoattractant, and CD40 ligand, showed a similar time course to that of the immunoglobulin kappa chain gene. We observed a heavy deposit of both IgM and IgG on the pathological neointima late in the development of transplant vasculopathy (i.e., 30 days after retransplantation) that was absent from the allografts immediately after retransplantation. CONCLUSION: During the development of transplant vasculopathy in a (donor x recipient) F1 environment, B cells were selectively recruited into the allografts and stimulated; meanwhile, antibodies against the pathological neointima were formed. These antibodies may be involved in the pathogenesis of transplant vasculopathy.

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PubMed2002

Selective chemokine and receptor gene expressions in allografts that develop transplant vasculopathy.

BACKGROUND: Chemokine systems probably play a role in transplant vasculopathy; however, a comprehensive study of the expression of chemokines and their receptors in this disease has not been performed. METHODS: The expression of all the rat chemokines and chemokine receptor genes for which the nucleotide sequences are known were quantitatively monitored using the fluorescence-based real-time reverse-transcriptase polymerase chain reaction technique, and selected cytokine-receptor pairs were determined using immunohistochemical staining. The analysis covered the whole time course of transplant vasculopathy in 2 different graft models (cardiac and aortic grafts) with 4 different strain combinations of rats. RESULTS: Among the 13 receptor genes examined, the CXCR3, CCR5, and CCR2 genes and those of their corresponding ligands were selectively and strongly induced in grafts that develop transplant vasculopathy. The expression patterns of the receptors were similar in both cardiac and aortic allografts, although their induction and their absolute levels of expression were amplified several fold in the grafted aorta compared with heart grafts. The genes were induced before morphologic changes became apparent and expression was sustained during the whole period of neointimal formation. Interestingly, immunohistochemical staining for CXCR3 showed a unique pattern of expression: we found weak expression on cells in the outer layer of the neointima and adventitia and found the strongest staining in the innermost layer of the neointima. CONCLUSIONS: This study suggested diagnostic as well as potential functional roles of the chemokine-receptor pairs IP10-CXCR3, RANTES-CCR5, and MCP1-CCR2 in rat models of transplant vasculopathy.

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