Tubule-derived exosomes play a central role in fibroblast activation and kidney fibrosis.

Kidney International
Xi LiuYouhua Liu

Abstract

Extracellular vesicles such as exosomes are involved in mediating cell-cell communication by shuttling an assortment of proteins and genetic information. Here, we tested whether renal tubule-derived exosomes play a central role in mediating kidney fibrosis. The production of exosomes was found to be increased in the early stage of unilateral ureteral obstruction, ischemia reperfusion injury or 5/6 nephrectomy models of kidney disease. Exosome production occurred primarily in renal proximal tubular epithelium and was accompanied by induction of sonic hedgehog (Shh). In vitro, upon stimulation with transforming growth factor-β1, kidney proximal tubular cells (HKC-8) increased exosome production. Purified exosomes from these cells were able to induce renal interstitial fibroblast (NRK-49F) activation. Conversely, pharmacologic inhibition of exosome secretion with dimethyl amiloride, depletion of exosome from the conditioned media or knockdown of Shh expression abolished the ability of transforming growth factor-β1-treated HKC-8 cells to induce NRK-49F activation. In vivo, injections of tubular cell-derived exosomes aggravated kidney injury and fibrosis, which was negated by an Shh signaling inhibitor. Blockade of exosome secretion...Continue Reading

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Citations

Jul 28, 2020·American Journal of Physiology. Renal Physiology·Jin WenZheng Dong
Nov 24, 2020·Hypertension·Olga Martinez-ArroyoRaquel Cortes
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Jun 18, 2021·Stem Cell Research & Therapy·Ruijie ZhangWentao Xu
Sep 3, 2021·Stem Cells International·Can JinHui Qian

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