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

A.P.C Balbi,R.S Costa,H.D.C Francescato,T.M Coimbra,E.C.S Marin

doi:10.1590/s0100-879x2009000100007

Abstract

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 (AT1) 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-week-old 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 AT1 and type 2 AII (AT2) 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.

Highlights

In humans, the branching ureteric duct reaches the outer cortex approximately 12 weeks before term
Α-smooth muscle actin (α-SMactin), proliferating cell nuclear antigen (PCNA), phosphoextracellular signal-regulated protein kinase (p-ERK), and angiotensin II (AII) expression are observed in the renal cortex of 1- and 7-day-old rats, followed by a decrease during renal development [3]
We observed a decrease in fibronectin, signaling and demonstrated that such activation is associ- α-SM-actin, PCNA, p-ERK Mitogen-activated protein kinases (MAPKs), AT1, and AII expression ated with acute ischemic-reperfusion injury and may be in the renal cortex of 1-day-old pups from dams subjected linked, in part, to AT2 stimulation

Summary

Introduction

The branching ureteric duct reaches the outer cortex approximately 12 weeks before term. Α-smooth muscle actin (α-SMactin), proliferating cell nuclear antigen (PCNA), phosphoextracellular signal-regulated protein kinase (p-ERK), and angiotensin II (AII) expression are observed in the renal cortex of 1- and 7-day-old rats, followed by a decrease during renal development [3]. The activation of the MAPK pathways by AII can result in apoptosis and cell proliferation and differentiation that are important events in renal development (Figure 2).

Results

Conclusion