Child Kidney Dis.  2017 Apr;21(1):1-7. 10.3339/jkspn.2017.21.1.1.

Mitogen-activated Protein Kinases in the Development of Normal and Diseased Kidneys

• Awazu M

• KMID: 2377561
• DOI: http://doi.org/10.3339/jkspn.2017.21.1.1

Abstract

Mitogen-activated protein kinases (MAPKs) play important roles in various cellular functions including proliferation, differentiation, and apoptosis. We showed that MAPKs are developmentally regulated in the rat kidney. p38 MAPK (p38) and extracellular signal-regulated kinase (ERK) were strongly expressed in the fetal kidney, whereas c-Jun N-terminal kinase (JNK) was detected predominantly in the adult kidney. The inhibition of p38 or ERK in organ culture resulted in reduced nephron formation with or without reduced kidney size. On the other hand, persistent fetal expression pattern of MAPKs, i.e., upregulation of p38 and ERK and downregulation of JNK, was observed in the cyst epithelium of human renal dysplasia, ovine fetal obstructive uropathy, and pcy mice, a model of polycystic kidney disease. Furthermore, activated p38 and ERK induced by cyclic stretch mediated proliferation and TGF-β1 expression in ureteric bud cells, probably leading to cyst formation and dysplastic changes. Inhibition of ERK slowed the disease progression in pcy mice. Finally, ERK and p38 were inactivated in the early embryonic kidney subjected to maternal nutrient restriction, characterized by reduced ureteric branching and nephron number. Thus, MAPKs mediate the development of normal and diseased kidney. Their modulation may result in novel therapeutic strategies against developmental abnormalities of the kidney.

Keyword

Extracellular signal-regulated kinase; p38 mitogen-activated protein kinase; c-Jun N-terminal kinase; Nephron; Dysplasia

MeSH Terms

Adult
Animals
Apoptosis
Disease Progression
Down-Regulation
Epithelium
Hand
Humans
JNK Mitogen-Activated Protein Kinases
Kidney*
Mice
Mitogen-Activated Protein Kinases*
Nephrons
Organ Culture Techniques
p38 Mitogen-Activated Protein Kinases
Phosphotransferases
Polycystic Kidney Diseases
Rats
Up-Regulation
Ureter
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
Phosphotransferases
p38 Mitogen-Activated Protein Kinases