Fluid shear stress induces renal epithelial gene expression through polycystin-2-dependent trafficking of extracellular regulated kinase

Daniel Flores, Lorenzo Battini, G. Luca Gusella, Rajeev Rohatgi

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Background: The cilium and cilial proteins have emerged as principal mechanosensors of renal epithelial cells responsible for translating mechanical forces into intracellular signals. Polycystin-2 (PC-2), a cilial protein, regulates flow/shear-induced changes in intracellular Ca2+ ([Ca 2+]i) and recently has been implicated in the regulation of mitogen-activated protein (MAP) kinases. We hypothesize that fluid shear stress (FSS) activates PC-2 which regulates MAP kinase and, in turn, induces MAP kinase-dependent gene expression, specifically, monocyte chemoattractant protein-1 (MCP-1). Methods: To test this, PC-2 expression was constitutively reduced in a murine inner medullary collecting duct (IMCD3) cell line, and the expression of FSS-induced MCP-1 expression and MAP kinase signaling compared between the parental (PC-2-expressing) and PC-2-deficient IMCD3 cells. Results: FSS induces MAP kinase signaling and downstream MCP-1 mRNA expression in wild-type IMCD3 cells, while inhibitors of MAP kinase prevented the FSS-induced MCP-1 mRNA response. In contradistinction, FSS did not induce MCP-1 mRNA expression in PC-2-deficient cells, but did increase activation of the upstream MAP kinases. Wild-type cells exposed to FSS augmented the nuclear abundance of activated MAP kinase while PC-2-deficient cells did not. Conclusions: PC-2 regulates FSS-induced MAP kinase trafficking into the nucleus of CD cells.

Original languageEnglish
Pages (from-to)p27-p36
JournalNephron - Physiology
Volume117
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • Extracellular regulated kinase
  • Fluid shear stress
  • IMCD3 cells
  • Mitogen-activated protein kinase
  • Polycystin-2
  • Renal epithelial gene expression

Fingerprint

Dive into the research topics of 'Fluid shear stress induces renal epithelial gene expression through polycystin-2-dependent trafficking of extracellular regulated kinase'. Together they form a unique fingerprint.

Cite this