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Expression of mitogen-activated protein kinases in human renal dysplasia
Sayu Omori1, Ryuji Fukuzawa, Mariko Hida
1Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Background:
We previously reported that the expression of mitogen-activated protein kinases (MAPKs) is developmentally regulated. Dysregulation of MAPKs may lead to kidney malformation. Thus, we investigated the expression of MAPKs in human renal dysplasia, one of the most common kidney malformations.
Methods:
Prenatal (gestational ages 20 to 36 weeks, N = 6) and postnatal (2 years old, N = 1) dysplastic kidneys, and normal kidneys (gestational ages 19 to 34 weeks, N = 4) were examined. Immunohistochemical studies were performed using antibodies against extracellular signal-regulated kinase (ERK), p38 MAPK (p38), c-Jun N-terminal kinase (JNK), phospho-MAPKs (P-MAPKs), and proliferating cell nuclear antigen (PCNA). Apoptosis was detected by the TUNEL method.
Results:
In dysplastic kidneys, proliferation was prominent in dysplastic tubules and also found in cyst epithelia. TUNEL staining was detected in dysplastic tubules and cysts, and occasionally in undifferentiated cells. p38 and anti-phospho-p38 (P-p38) were strongly expressed in dysplastic epithelia, but not detected in normal kidneys at any stage examined. On the other hand, JNK and P-JNK were positive in tubular epithelia of normal kidneys, whereas their expression was barely detectable in dysplastic tubules and cysts. ERK was expressed in all tubular segments, and P-ERK was detected in distal tubules and collecting ducts of normal kidneys. Dysplastic kidney epithelia stained exclusively positive for ERK and P-ERK.
Conclusions:
p38 is ectopically expressed, and JNK is down-regulated in dysplastic kidney epithelia. Furthermore, dysplastic epithelia are exclusively positive for ERK and P-ERK. Activated p38 and ERK may mediate hyperproliferation of dysplastic tubules resulting in cyst formation, whereas down-regulated JNK expression may be the cause or the result of an undifferentiated state of dysplastic epithelia.
Insights
Mitogen-activated protein kinases (MAPKs) are involved in kidney development. This study found abnormal MAPK expression, including p38 and ERK, in human renal dysplasia, suggesting a role in malformation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Nephrology
Background:
- Mitogen-activated protein kinases (MAPKs) expression is developmentally regulated.
- Dysregulation of MAPKs can lead to kidney malformations.
- Human renal dysplasia is a common congenital kidney malformation.
Purpose of the Study:
- Investigate the expression of MAPKs in human renal dysplasia.
- Determine the role of MAPKs in kidney malformation.
Main Methods:
- Examined prenatal and postnatal human dysplastic and normal kidneys.
- Utilized immunohistochemistry for ERK, p38 MAPK, JNK, and PCNA.
- Assessed apoptosis using TUNEL staining.
Main Results:
- Dysplastic kidneys showed prominent proliferation in tubules and cysts.
- p38 MAPK and phospho-p38 were highly expressed in dysplastic epithelia, but absent in normal kidneys.
- JNK and phospho-JNK were down-regulated in dysplastic kidneys, while ERK and phospho-ERK were exclusively expressed in dysplastic epithelia.
Conclusions:
- p38 MAPK is ectopically expressed, and JNK is down-regulated in dysplastic kidney epithelia.
- ERK and phospho-ERK are exclusively expressed in dysplastic epithelia.
- Activated p38 and ERK may drive hyperproliferation and cyst formation in renal dysplasia, while down-regulated JNK may indicate an undifferentiated state.