ERK and p38 MAP kinase are required for rat renal development

Hida, Mariko; Omori, Sayu; Awazu, Midori

doi:10.1046/j.1523-1755.2002.00273.x

Cited by 52 publications

(65 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role of JNK MAPK in embryogenesis has been investigated, and it has been shown that the loss of the MKK4 gene, a JNK activator, results in embryonic death (26). A decrease in glomerulus number was observed in 15-day-old embryos cultured for 48 and 120 h with ERK or p38 inhibitors (27). Choi et al (15) reported that the treatment of newborn rats with enalapril for 7 days increased JNK-2 and p38 MAPK expression in the kidney, and that these increases were temporally associated with higher numbers of apoptotic cells.…”

Section: Evidence For the Role Of Mapk In Kidney Developmentmentioning

confidence: 99%

Roles of mitogen-activated protein kinases and angiotensin II in renal development

Balbi

Francescato

Marin

et al. 2009

Braz J Med Biol Res

View full text Add to dashboard Cite

Experimental and clinical evidence suggests that angiotensin II (AII) participates in renal development. Renal AII content is several-fold higher in newborn rats and mice than in adult animals. AII receptors are also expressed in higher amounts in the kidneys of newborn rats. The kidneys of fetuses whose mother received a type 1 AII receptor (AT 1 ) antagonist during gestation present several morphological alterations. Mutations in genes that encode components of the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Morphological changes were detected in the kidneys of 3-weekold angiotensin-deficient mice. Mitogen-activated protein kinases (MAPKs) are important mediators that transduce extracellular stimuli to intracellular responses. The MAPK family comprises three major subgroups, namely extracellular signal-regulated protein kinase (ERK), c-jun N-terminal kinases (JNK), and p38 MAPK (p38). Important events in renal growth during nephrogenesis such as cellular proliferation and differentiation accompanied by apoptosis on a large scale can be mediated by MAPK pathways. A decrease in glomerulus number was observed in embryos cultured for 48 and 120 h with ERK or p38 inhibitors. Many effects of AII are mediated by MAPK pathways. Treatment with losartan during lactation provoked changes in renal function and structure associated with alterations in AT 1 and type 2 AII (AT 2 ) receptors and p-JNK and p-p38 expression in the kidney. Several studies have shown that AII and MAPKs play an important role in renal development. However, the relationship between the effects of AII and MAPK activation on renal development is still unclear.

show abstract

Section: Evidence For the Role Of Mapk In Kidney Developmentmentioning

confidence: 99%

Roles of mitogen-activated protein kinases and angiotensin II in renal development

Balbi

Francescato

Marin

et al. 2009

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…Among these, extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38) are required for nephrogenesis, metanephros growth, and ureteric bud branching (10)(11)(12). On the other hand, phosphatidylinositol 3-kinase (PI3K) and Akt, downstream signaling molecules of Ret, the kinase subunit of the glial cell line-derived neurotrophic factor (GDNF) receptor, promote branching morphogenesis (13).…”

mentioning

confidence: 99%

Maternal nutrient restriction inhibits ureteric bud branching but does not affect the duration of nephrogenesis in rats

Awazu

Hida

2015

Pediatr Res

Self Cite

View full text Add to dashboard Cite

Background: Maternal nutrient restriction produces offspring with fewer nephrons. We studied whether the reduced nephron number is due to the inhibition of ureteric branching or early cessation of nephrogenesis in rats. Signaling pathways involved in kidney development were also examined. Methods: The offspring of dams given food ad libitum (control (CON)) and those subjected to 50% food restriction (nutrient restriceted (NR)) were examined. results: At embryonic day 13 (E13), there was no difference between NR and CON in body weight or kidney size. Ureteric buds branched once in both NR and CON. At E14 and E15, body and kidney size were significantly reduced in NR. Ureteric bud tip numbers were also reduced to 50% of CON. On the other hand, the disappearance of nephrogenic zone and a nephron progenitor marker Cited1 was not different between CON and NR. The final glomerular number of NR was 80% of CON. Activated extracellular signal-regulated kinase (ERK), p38, PI3K, Akt, and mammallian target of rapamycin (mTOR), and protein expression of β-catenin were downregulated at E15. conclusion: Ureteric branching is inhibited and developmentally regulated signaling pathways are downregulated at an early stage by maternal nutrient restriction. These changes, not early cessation of nephrogenesis, may be a mechanism for the inhibited kidney growth and nephrogenesis. t he concept that disturbed intrauterine organogenesis affects the health and disease in the adulthood, termed developmental origins of health and disease, has been increasingly recognized. With respect to the kidney, low birth weight is associated with a risk for hypertension and renal disease, and reduced nephron number is considered to be the cause. In animals, maternal protein or global nutrient restriction, uterine artery ligation, hyperglycemia, and exposure to various agents such as glucocorticoids or alcohol produce offspring with fewer nephrons (1-6). Depletion of stem cells by increased apoptosis has been suggested to be responsible for the decreased nephron formation (1,3). On the other hand, ureteric bud branching is a fundamental step in determining nephron number. The mechanism of reduced nephron endowment in dexamethasone or ethanol exposure has been suggested to be inhibited branching morphogenesis in an organ culture study (5,7). Reduced ureteric branching has recently been reported in a model of maternal hyperglycemia in vivo (8).Another possible mechanism of reduced nephron number is early cessation of nephrogenesis. In human premature infants, nephrogenesis is reported to continue only up to 40 d after birth (9). These infants are under various stresses including hypoxia, infection, and medications adversely affecting nephrogenesis. It has been postulated that adverse conditions during development promote differentiation aiming at early maturation and survival at the expense of reduced organ growth. Newborn rats resemble human premature neonates in that nephrogenesis continues after birth. Early cessation of nephrogenesis, therefore, may b...

show abstract

“…This is reminiscent of the metanephroi cultured with SB203580 in our previous study, in which WT1‐positive cells were distributed loosely in mesenchyme with slight signs of condensation around ureteric buds (Hida et al. 2002). Furthermore, SB203580‐treated metanephroi were small with reduced glomerular number.…”

Section: Discussionmentioning

confidence: 99%

“…These features are similar to metanephroi cultured with an inhibitor of p38 mitogen‐activated protein kinase (p38) as previously reported (Hida et al. 2002). BMP7 has been reported to be necessary for the maintenance of nephron progenitor cells through another member of MAP kinase c‐Jun N‐terminal kinase (JNK) (Blank et al.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

BMP7 dose-dependently stimulates proliferation and cadherin-11 expression via ERK and p38 in a murine metanephric mesenchymal cell line

2017

Self Cite

View full text Add to dashboard Cite

BMP7 is expressed in ureteric buds and cap mesenchyme of the fetal kidney, mediating branching morphogenesis and survival and priming of metanephric mesenchyme. Although dose‐dependent effects of BMP7 in collecting duct cells have been reported, studies in metanephric mesenchymal cells are lacking. We examined the effects of BMP7 on MAP kinase activation, proliferation, and expression of cadherins in a metanephric mesenchymal cell line MS7 by thymidine incorporation, immunoblot analysis, and quantitative real‐time PCR. The levels of phosphorylated ERK (P‐ERK) and phosphorylated p38 (P‐p38) were not altered at 10 min, 1 h, and 6 h with low‐dose BMP7 (0.25 nmol/L), but were increased at 24 h. At 24 h, P‐ERK was increased with low‐dose BMP7, but not by intermediate‐ (1 nmol/L) or high‐dose (10 nmol/L) BMP7, whereas p38 was activated by intermediate‐dose BMP7. Cell proliferation of MS7 was significantly increased by low‐ and intermediate‐dose BMP7 and decreased by high‐dose BMP7. A p38 inhibitor SB203580 5 μmol/L or a MEK inhibitor PD98059 5 μmol/L abolished BMP7‐stimulated proliferation. Expression of cadherin‐11, an adhesion molecule known to promote cell migration and compaction, was upregulated by intermediate‐dose BMP7. BMP7‐induced cadherin‐11 expression was inhibited by cotreatment with SB203580 and PD98059. Finally, in metanephroi cultured with siRNA for cadherin‐11, the number and thickness of cap mesenchyme were reduced. In conclusion, BMP7 exerts differential effects depending on the concentration; it may expand mesenchymal cells in the stroma where BMP7 concentration is low and may upregulate cadherin‐11 promoting condensation around the tip of ureteric buds.

show abstract

ERK and p38 MAP kinase are required for rat renal development

Abstract: Both ERK and p38 are required for renal development. ERK appears to play a role in nephrogenesis and p38 for kidney growth and nephrogenesis.

Cited by 52 publications

References 27 publications

Roles of mitogen-activated protein kinases and angiotensin II in renal development

Roles of mitogen-activated protein kinases and angiotensin II in renal development

Maternal nutrient restriction inhibits ureteric bud branching but does not affect the duration of nephrogenesis in rats

BMP7 dose-dependently stimulates proliferation and cadherin-11 expression via ERK and p38 in a murine metanephric mesenchymal cell line

Contact Info

Product

Resources

About