Hedgehog signaling indirectly affects tubular cell survival after obstructive kidney injury

Alysha A. Rauhauser, Chongyu Ren, Dongmei Lu, Binghua Li, Jili Zhu, Kayla McEnery, Komal Vadnagara, Diana Zepeda-Orozco, Xin J. Zhou, Fangming Lin, Anton M. Jetten, Massimo Attanasio

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Hedgehog (Hh) is an evolutionary conserved signaling pathway that has important functions in kidney morphogenesis and adult organ maintenance. Recent work has shown that Hh signaling is reactivated in the kidney after injury and is an important mediator of progressive fibrosis. Pericytes and fibroblasts have been proposed to be the principal cells that respond to Hh ligands, and pharmacological attenuation of Hh signaling has been considered as a possible treatment for fibrosis, but the effect of Hh inhibition on tubular epithelial cells after kidney injury has not been reported. Using genetically modified mice in which tubule-derived hedgehog signaling is increased and mice in which this pathway is conditionally suppressed in pericytes that express the proteoglycan neuron glial protein 2 (NG2), we found that suppression of Hh signaling is associated with decreased macrophage infiltration and tubular proliferation but also increased tubular apoptosis, an effect that correlated with the reduction of tubular β-catenin activity. Collectively, our data suggest a complex function of hedgehog signaling after kidney injury in initiating both reparative and proproliferative, prosurvival processes.

Original languageEnglish (US)
Pages (from-to)F770-F778
JournalAmerican Journal of Physiology - Renal Physiology
Volume309
Issue number9
DOIs
StatePublished - Jan 1 2015

Keywords

  • Hedgehog signaling
  • Kidney injury
  • UUO

ASJC Scopus subject areas

  • Physiology
  • Urology

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    Rauhauser, A. A., Ren, C., Lu, D., Li, B., Zhu, J., McEnery, K., Vadnagara, K., Zepeda-Orozco, D., Zhou, X. J., Lin, F., Jetten, A. M., & Attanasio, M. (2015). Hedgehog signaling indirectly affects tubular cell survival after obstructive kidney injury. American Journal of Physiology - Renal Physiology, 309(9), F770-F778. https://doi.org/10.1152/ajprenal.00232.2015