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

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 (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.

The Effect of Electroacupuncture on Insulin-Like Growth Factor-I and Oxidative Stress in an Animal Model of Renal Failure-Induced Hypertension

“…Other studies have reported that rats with RF-induced hypertension exhibit apoptosis and oxidative stress in the kidney and that oxidative stress in the kidney and serum decrease IGF-I secretion [39,40,41,42,43,44,45]. This work showed an increase in IGF-I levels following EA stimulation at the ST36 and KI3 acupoints, suggesting that EA could activate IGF-I during RF-induced hypertension.…”

Long-term exercise attenuates blood pressure responsiveness and modulates kidney angiotensin II signalling and urinary sodium excretion in SHR

“…43 Several effects of AngII are mediated through mitogen-activated protein kinases (MAPK) pathways. [48][49][50] Kubo et al 48 reported that AngII provokes increased MAPK activity in cultures of vascular smooth muscle cells, and that this activity is inhibited by losartan. It has been previously shown that p-ERK is related to cell proliferation and differentiation, while p-JNK and p38 MAPKs are involved in apoptosis.…”

Chronic treatment with lisinopril decreases proliferative and apoptotic pathways in autosomal recessive polycystic kidney disease

“…Moreover, inhibitors of the RAS, such as angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), are primary drug options prescribed to treat the symptoms associated with ARPKD. ANGII can exert many of its biological functions in the kidney through the activation of a group of mitogen activated protein kinases (MAPKs) [8]. The classical MAPK pathway includes the extracellular signal-regulated kinases 1 (ERK1) and 2 (ERK2) and has been extensively studied in polycystic kidney disease (PKD) as one of the main proliferative signaling pathways involved in mediating epithelial cell proliferation and cyst formation [9].…”