Enhanced Hyaluronan Synthesis in the MRL-Faslpr Kidney: Role of Cytokines
| Autor: | Beatrice Beck-Schimmer, Rudolf P. Wüthrich, Beat Oertli, Li-kang Sun, Ernst Feusi, Anita Sibalic |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Kidney business.industry medicine.medical_treatment Extracellular matrix component medicine.disease Cell biology Nephropathy Extracellular matrix Transplantation Pathogenesis chemistry.chemical_compound Endocrinology medicine.anatomical_structure Cytokine chemistry Internal medicine Hyaluronic acid medicine business |
| Zdroj: | Nephron. 83:66-73 |
| ISSN: | 2235-3186 1660-8151 |
| DOI: | 10.1159/000045475 |
| Popis: | Background/Aim: Pathological accumulation of the extracellular matrix component hyaluronan (HA) occurs in the kidney cortex in immune-system mediated tissue injury. The purpose of the present study was to examine the pattern of HA deposition and the mechanisms of HA synthesis in the MRL-Faslpr mouse model of lupus nephritis. Methods: Kidneys from normal and autoimmune mice were examined for HA content by immunofluorescence staining. Steady state mRNA levels for key enzymes involved in HA synthesis – uridine diphosphate-glucose dehydrogenase (UDPGDH) and HA synthases (HAS) 1, 2 and 3 – were assessed by reverse-transcriptase polymerase chain reaction (RT-PCR). Using cultured mouse tubular epithelial cells, the regulation of the HA production in vitro in response to tumor necrosis factor alpha and interferon gamma was also examined. Results: By immunofluorescence staining, large amounts of HA were detected in the cortical interstitium of MRL-Faslpr mice with autoimmune renal injury, but not in congenic MRL-++ mice. By RT-PCR the presence of transcripts for several genes involved in the synthesis of HA in normal and autoimmune kidneys could be demonstrated, including mRNA for UDPGDH and HAS1 and HAS2, but not for HAS3. Except for HAS2, steady state mRNA levels for these enzymes did not correlate with disease activity. Analyzing a kidney tubular epithelial cell line in vitro, it was found that tumor necrosis factor alpha and interferon gamma, and particularly the combination of these two cytokines, markedly enhanced the synthesis of HA. The expression of HAS2 mRNA was also enhanced in response to cytokine treatment. Conclusions: HA deposition is prominent in MRL-Faslpr mice with renal disease and could be mediated by local synthesis through HAS1 and HAS2. We hypothesize that the enhanced synthesis of HA could be promoted by proinflammatory cytokines in vivo. The functional significance of HA accumulation in autoimmune renal injury remains to be determined. |
| Databáze: | OpenAIRE |
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