Regulation of collagen type IV genes is organ-specific: Evidence from a canine model of Alport syndrome
| Autor: | Keqin Zheng, Billy G. Hudson, Robert M. Jacobs, Scott J. Harvey, Barbara Jefferson, Paul S. Thorner, Julie Perry, Yoshikazu Sado, Yoshifumi Ninomiya |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Nephrology kidney Pathology medicine.medical_specialty LIM-Homeodomain Proteins Nephritis Hereditary testis Biology collagen type IV 03 medical and health sciences Type IV collagen Dogs 0302 clinical medicine Internal medicine Gene expression medicine Animals RNA Messenger Alport syndrome 030304 developmental biology Homeodomain Proteins 0303 health sciences Kidney Glomerulosclerosis Glomerulonephritis Blotting Northern medicine.disease Immunohistochemistry Disease Models Animal medicine.anatomical_structure Endocrinology Organ Specificity 030220 oncology & carcinogenesis gene expression Transcription Factors Kidney disease |
| Zdroj: | Kidney International. 68:2121-2130 |
| ISSN: | 0085-2538 |
| DOI: | 10.1111/j.1523-1755.2005.00668.x |
| Popis: | Regulation of collagen type IV genes is organ-specific: Evidence from a canine model of Alport syndrome . Background Despite advances in knowledge about collagen type IV at the protein level, little is known about expression of its six α chains. X-linked Alport syndrome provides a system to study collagen type IV gene expression within a setting of disturbed protein synthesis. Mutations in the α5 chain result in loss of the α3/α4/α5 and α1/α2/α5/α6 networks from the kidney, with progressive renal disease. Methods We used a canine model of Alport syndrome to measure expression of the six type IV collagen chains from 11 days to 71/2 months of age. We determined to what extent message levels in kidney change over time, and what correlation exists with clinical and pathologic changes in glomeruli, and the primary mutation. The latter was evaluated by examining testis, an organ normally containing the same collagen type IV networks but uninvolved by disease. Results The α1 to α6 mRNAs were expressed at all time points in normal canine kidney. By comparison to normal, in Alport dog kidney, the α1 and α2 mRNAs were up-regulated after 2 months of age, α3 and α4 mRNAs were down-regulated by 2 months of age, and the α5 mRNA was almost undetectable at any time. In testis, all mRNAs were expressed at comparable levels in normal and affected dogs other than the α5 chain, which was not expressed in affected testis. Conclusion Normal expression of collagen type IV is under control mechanisms specific to each organ and to individual chains. The altered expression in canine Alport syndrome is not the direct result of the mutation, since these changes do not occur in all organs nor are they present from birth. Instead, collagen type IV expression is influenced by disease, with down-regulation of α3 and α4 chains temporally related to the onset of proteinuria, and up-regulation of α1 and α2 chains to glomerulosclerosis. This dysregulation of the α3 and α4 chains is unique to this Alport model, and suggests an unidentified mechanism linking pathology with down-regulation of expression of these two chains. |
| Databáze: | OpenAIRE |
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