Basic ResearchTubule-derived exosomes play a central role in fibroblast activation and kidney fibrosis
Graphical abstract
Section snippets
Increased biogenesis of exosomes and microvesicles in various models of CKD
We first examined the production of extracellular vesicles in various models of CKD induced by unilateral ureteral obstruction (UUO), ischemia-reperfusion injury (IRI), and 5/6 nephrectomy, respectively. As shown in Figure 1a to d, renal expression of CD63, a marker of exosomes that is associated with membranes of intracellular vesicles,16 was upregulated after UUO or IRI. Time-course studies revealed that CD63 started to increase as early as day 1 and continued to increase along with the
Discussion
Kidney tubular epithelium is vulnerable to various metabolic, ischemic, and toxic insults. The injured and/or stressed tubular epithelial cells often engage multiple intercellular crosstalks with interstitial fibroblasts, leading to their activation and expansion.4,36 Such epithelial-mesenchymal communication (EMC) has become a new paradigm in renal fibrogenesis.27,37 In the present study, we show that extracellular vesicles, particularly exosomes, play an essential role in mediating EMC in
Animal model
Male C57BL/6 mice were purchased from Vital River Laboratory (Beijing, China) and housed with free access to water and chow diet. For the UUO model, mice were subjected to double-ligating left ureter following a midline abdominal incision. UIRI was established as described.26 Briefly, left renal pedicles were clipped for 35 minutes using microaneurysm clamps. The intact right kidney was removed at 10 days post-UIRI, and then mice were sacrificed a day after.46 The kidney tissues were collected
Disclosure
All the authors declared no competing interests.
Acknowledgments
This work was supported by the National Natural Science Foundation of China grants 81521003, 81700652, and 81722011 and Guangzhou Regenerative Medicine and Health Guangdong Laboratory grants 2018GZR110104001, 2018GZR0202003, and 2018GZR110102004.
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