Cyclic AMP prevents decrease of phosphorylated ezrin/radixin/moesin and chloride intracellular channel 5 expressions

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Hua Tao1, Xiaoying Li1, Kai Wei1

  • 1Renal Division and Molecular Cell Lab for Kidney Disease, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160#, Pu Jian Road, Shanghai, 200001, China.

Clinical and Experimental Nephrology
|March 2, 2015
PubMed
Abstract

Insights

Cyclic AMP (cAMP) signaling protects podocytes from injury by improving ezrin/radixin/moesin (ERM) phosphorylation and chloride intracellular channel 5 (CLIC5) expression. Forskolin, a cAMP activator, alleviates albuminuria in a mouse model of nephrosis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Cyclic AMP (cAMP) signaling is implicated in protecting podocytes from injury.
  • The precise molecular mechanisms underlying cAMP-mediated podocyte protection remain unclear.
  • This study investigates the role of forskolin in modulating key proteins in injured podocytes.

Purpose of the Study:

  • To explore the effects of forskolin, an adenylate cyclase agonist, on ezrin/radixin/moesin (ERM) phosphorylation and chloride intracellular channel 5 (CLIC5) expression in podocytes.
  • To elucidate the molecular pathways involved in cAMP-mediated protection against podocyte injury.

Main Methods:

  • Adriamycin (ADR)-induced nephrosis model in BalB/C mice.
  • Forskolin pretreatment in ADR-induced nephrosis.
  • Assessment of albuminuria using urine Coomassie blue stain.
  • Confocal microscopy and western blotting to measure nephrin, synaptopodin, CLIC5, and phosphorylated ERM (p-ERM).
  • In vitro studies using podocytes treated with cAMP analogues and Rho inhibitor.

Main Results:

  • Forskolin treatment partially reduced albuminuria and foot process effacement in ADR-induced nephrosis.
  • ADR-induced decreases in nephrin, synaptopodin, p-ERM, and CLIC5 were restored by forskolin.
  • PKA-selective cAMP analogue prevented puromycin aminonucleoside (PAN)-induced CLIC5 downregulation.
  • Epac-selective cAMP analogue blocked PAN-induced p-ERM downregulation.
  • PAN-induced RhoA activation was inhibited by pCPT-cAMP, and Rho inhibition decreased CLIC5 expression.

Conclusions:

  • Activation of cAMP signaling may attenuate albuminuria in ADR-induced nephrosis.
  • Distinct downstream signaling pathways likely mediate the protective effects of cAMP on CLIC5 and p-ERM expression, respectively.
Keywords:
ActinAlbuminurineCytoskeleton

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