Mitogen-activated Protein Kinases in the Development of Normal and Diseased Kidneys
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (31)
- Schaeffer HJ, "Mitogen-activated protein kinases:specific messages from ubiquitous messengers", Mol Cell Biol, 19, pp.2435~2444 (1999)
- Xia Z, "Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis", Science, 270, pp.1326~1331 (1995)
- Omori S, "Expression of mitogen-activated protein kinase family in rat renal development", Kidney Int, 58, pp.27~37 (2000)
- Hida M, "ERK and p38 MAP kinase are required for rat renal development", Kidney Int, 61, pp.1252~1262 (2002)
- Omori S, "Extracellular signal-regulated kinase inhibition slows disease progression in mice with polycystic kidney disease", J Am Soc Nephrol, 17, pp.1604~1614 (2006)
- Omori S, "Expression of mitogenactivated protein kinases in human renal dysplasia", Kidney Int, 61, pp.899~906 (2002)
- Omori S, "Activated extracellular signal-regulated kinase correlates with cyst formation and transforming growth factor-beta expression in fetal obstructive uropathy", Kidney Int, 73, pp.1031~1037 (2008)
- Fisher CE, "Erk MAP kinase regulates branching morphogenesis in the developing mouse kidney", Development, 128, pp.4329~4338 (2001)
- Ihermann-Hella A, "Mitogen-activated protein kinase (MAPK) pathway regulates branching by remodeling epithelial cell adhesion", PLoS Genet, 10, pp.e1004193~ (2014)
- Smeeton J, "Integrin-linked kinase controls renal branching morphogenesis via dual specificity phosphatase 8", J Am Soc Nephrol, 27, pp.1465~1477 (2016)
- Osafune K, "Identification of multipotent progenitors in the embryonic mouse kidney by a novel colony-forming assay", Development, 133, pp.151~161 (2006)
- Blank U, "BMP7 promotes proliferation of nephron progenitor cells via a JNK-dependent mechanism", Development, 136, pp.3557~3566 (2009)
- Peters CA, "Obstruction of the fetal urinary tract", J Am Soc Nephrol, 8, pp.653~663 (1997)
- Winyard PJ, "The PAX2tanscription factor is expressed in cystic and hyperproliferative dysplastic epithelia in human kidney malformations", J Clin Invest, 98, pp.451~459 (1996)
- Kitagawa H, "Early bladder wall changes after creation of obstructive uropathy in the fetal lamb", Pediatr Surg Int, 22, pp.875~879 (2006)
- Fujita H, "Cyclic stretch induces proliferation and TGF-β1-mediated apoptosis via p38 and ERK in ureteric bud cells", Am J Physiol Renal Physiol, 299, pp.F648~F655 (2010)
- Olbrich H, "Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis", Nat Genet, 34, pp.455~459 (2003)
- Ohashi R, "Inhibition of p38 mitogen-activated protein kinase augments progression of remnant kidney model by activating the ERK pathway", Am J Pathol, 164, pp.477~485 (2004)
- Awazu M, "Maternal nutrient restriction inhibits ureteric bud branching but does not affect the duration of nephrogenesis in rats", Pediatr Res, 77, pp.633~639 (2015)
- Henry TQ, "GDNF and MAPK-ERK pathway signaling is reduced during nephrogenesis following maternal undernutrition", J Dev Orig Health Dis, 1, pp.67~74 (2010)
- Pozzi A, "H-Ras, RRas, and TC21 differentially regulate ureteric bud cell branching morphogenesis", Mol Biol Cell, 17, pp.2046~2056 (2006)
- Usui J, "Murine metanephric mesenchyme possesses characteristics of vascular endothelial cells in vitro", Nephron Exp Nephrol, 102, pp.e93~e98 (2006)
- Piscione TD, "BMP7 controls collecting tubule cell proliferation and apoptosis via Smad1-dependent and -independent pathways", Am J Physiol Renal Physiol, 280, pp.F19~F33 (2001)
- Kazama I, "Podocyte-derived BMP7 is critical for nephron development", J Am Soc Nephrol, 19, pp.2181~2191 (2008)
- Awazu M, "Mechanisms of mitogenactivated protein kinase activation in experimental diabetes", J Am Soc Nephrol, 10, pp.738~745 (1999)
- Fujita H, "ERK and p38mediate high-glucose-induced hypertrophy and TGF-β expression in renal tubular cells", Am J Physiol Renal Physiol, 286, pp.F120~F126 (2004)
- Feliers D, "Erk in kidney diseases", J Signal Transduct, pp.768512~ (2011)
- Stambe C, "The role of p38α mitogen-activated protein kinase activation in renal fibrosis", J Am Soc Nephrol, 15, pp.370~379 (2004)
- Furuichi K, "Administration of FR167653, a new anti-inflammatory compound, prevents renal ischaemia", reperfusion injury in mice, 2002, pp.17, 399~407
- Ozaki KI, "Targeting the ERK signaling pathway as a potential treatment for insulin resistance and type 2 diabetes", Am J Physiol Endocrinol Metab, 310, pp.E643~E651 (2016)
- Nutter FH, "Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis", PLoS One, 10, pp.e0137321~ (2015)