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

Abstract

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

JNK Signalling Regulates Self-Renewal of Proliferative Urine-Derived Renal Progenitor Cells via Inhibition of Ferroptosis

“…JNK is part of the mitogen-activated protein kinase (MAPK) family and each pathway is a sequential activation of MAPKKKs [8]. This pathway is involved in various processes such as proliferation and survival as well as stress and inflammation-induced apoptosis and is also linked to acute and chronic kidney diseases [9][10][11][12]. In nephron progenitor cells, JNK signalling plays a major role in maintaining the progenitor fate.…”

JNK signalling regulates self-renewal of proliferative urine-derived renal progenitor cells via inhibition of ferroptosis

“…JNK is part of the mitogen-activated protein kinase (MAPK) family and each pathway is a sequential activation of MAPKKKs (Javelaud and Mauviel, 2005). This pathway is involved in various processes such as proliferation, survival as well as stress and inflammation-induced apoptosis and is also linked to acute and chronic kidney diseases (Awazu, 2017; Engel et al, 1999; Smith et al, 2021; Tournier et al, 2000). In nephron progenitor cells JNK signalling plays a major role in maintaining the progenitor fate.…”