ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: FR-PO601

Chronic Fluid Shear Stress (FSS) Induces ERK Dependent Sodium Transport in Principal Cells (PCs)

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic


  • Repetti, Robert Lawrence, Northport VAMC, Northport, New York, United States
  • Meth, Jennifer, Northport VAMC, Northport, New York, United States
  • Majumder, Nomrota, Stony Brook University School of Medicine, Stony Brook, New York, United States
  • Sharma, Mukut, KCVA Medical Center, Kansas City, Missouri, United States
  • Srivastava, Tarak, Childrens's Mercy Hospital, Kansas City, Missouri, United States
  • Rohatgi, Rajeev, Northport VAMC, Northport, New York, United States

Nephron loss by disease or nephrectomy lead to compensatory hemodynamic and cellular effects on the remaining nephrons. Increases in single nephron glomerular filtration rate and tubular flow rate, exert FSS on tubular epithelia. Rising tubular flow rate have acute and chronic effects on epithelial Na channel (ENaC) dependent Na absorption. Acute (minutes) increase in cortical collecting duct (CCD) flow rate augments Na absorption; however, chronic (hours) flow, as in unilateral nephrectomy, is expected to augment Na excretion and increase fractional excretion of Na. In vitro FSS induces ERK phosphorylation in murine CD cells and ERK has been shown to be a regulator of ENaC. Thus, we hypothesize that chronic FSS-induces ERK activation in the CCD to inhibit amiloride sensitive Na transport.


To test this, murine PCs (mpkccd) were grown on snapwells under static conditions or exposed to 0.4 dynes/cm2 of FSS for 24 hrs and amiloride sensitive Na current (Iasc) measured in an Ussing chamber. Kidneys from sham control and unilateral nephrectomized mice were used for immunohistochemistry (IHC) and immunofluorescence (IF).


Iasc was 23.4±1.4 μA/cm2 (n=6) in static PCs, but in cells exposed to 24 hours of FSS the Iasc was reduced to 12.9±1.0 μA/cm2 (n=9; p<0.01). Next, we tested whether U0126, a MEK inhibitor, could recover the FSS mediated reduction in Iasc. PCs exposed to FSS and U0126 exhibited a lower Iasc of 6.9±0.3 µA/cm2 (n=4, p<0.01 vs static and FSS without inhibitor), suggesting ERK stimulates ENaC dependent transport and that non-ERK factors repress Iasc. To identify ERK expression in vivo, we performed IHC and IF in kidneys of mice post-unilateral nephrectomy and in sham controls. IHC, in control and nephrectomized mice, showed heterogenous expression of phospho-ERK (pERK) in the CCD. Sham and nephrectomized kidneys were labelled with dolichos biflorus agglutinin (DBA), a PC marker, and anti-pERK antibody. In sham kidneys pERK co-localized with PC cells; however, in nephrectomized mice pERK chiefly co-localized with DBA and in a minority of cells localized with non-DBA stained cells of the CCD.


Chronic FSS induces ERK to stimulate ENaC dependent Na transport in vitro, and in vivo pERK is expressed primarily in PCs, suggesting ERK may play an identical role in vivo


  • Veterans Affairs Support