TY - JOUR
T1 - miRNA profiling of urinary exosomes to assess the progression of acute kidney injury
AU - Sonoda, Hiroko
AU - Lee, Byung Rho
AU - Park, Ki Hoon
AU - Nihalani, Deepak
AU - Yoon, Je Hyun
AU - Ikeda, Masahiro
AU - Kwon, Sang Ho
N1 - Funding Information:
This work was supported by a Carl Gottschalk career development award (American Society of Nephrology) and a Pilot Discovery grant (Center for Genomic Medicine, MUSC) to S.-H. K. The sequencing analysis was supported in part by Genomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina (P30CA138313) and MUSC bioinformatics core, Center for Genomic Medicine. This work was supported by the American Society of Nephrology [the Carl Gottschalk Award to S.-H. K.; the Center for Genomic Medicine, SCTR [the Pilot Discovery grant to S.-H. K.]; Augusta University [startup package to S.-H. K.] and the JSPS KAKENHI [15H04594, 16K15047, 18H02348 to M.I., 15K18784, 18K05996 to H.S.].
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Because exosomes have gained attention as a source of biomarkers, we investigated if miRNAs in exosomes (exo-miRs) can report the disease progression of organ injury. Using rat renal ischemia-reperfusion injury (IRI) as a model of acute kidney injury (AKI), we determined temporally-released exo-miRs in urine during IRI and found that these exo-miRs could reliably mirror the progression of AKI. From the longitudinal measurements of miRNA expression in kidney and urine, we found that release of exo- miRs was a regulated sorting process. In the injury state, miR-16, miR-24, and miR-200c were increased in the urine. Interestingly, expression of target mRNAs of these exo-miRs was significantly altered in renal medulla. Next, in the early recovery state, exo-miRs (miR-9a, miR-141, miR-200a, miR-200c, miR-429), which share Zeb1/2 as a common target mRNA, were upregulated together, indicating that they reflect TGF-β-associated renal fibrosis. Finally, release of exo-miRs (miR-125a, miR-351) was regulated by TGF-β1 and was able to differentiate the sham and IRI even after the injured kidneys were recovered. Altogether, these data indicate that exo-miRs released in renal IRI are associated with TGF-β signaling. Temporal release of exo-miRs which share targets might be a regulatory mechanism to control the progression of AKI.
AB - Because exosomes have gained attention as a source of biomarkers, we investigated if miRNAs in exosomes (exo-miRs) can report the disease progression of organ injury. Using rat renal ischemia-reperfusion injury (IRI) as a model of acute kidney injury (AKI), we determined temporally-released exo-miRs in urine during IRI and found that these exo-miRs could reliably mirror the progression of AKI. From the longitudinal measurements of miRNA expression in kidney and urine, we found that release of exo- miRs was a regulated sorting process. In the injury state, miR-16, miR-24, and miR-200c were increased in the urine. Interestingly, expression of target mRNAs of these exo-miRs was significantly altered in renal medulla. Next, in the early recovery state, exo-miRs (miR-9a, miR-141, miR-200a, miR-200c, miR-429), which share Zeb1/2 as a common target mRNA, were upregulated together, indicating that they reflect TGF-β-associated renal fibrosis. Finally, release of exo-miRs (miR-125a, miR-351) was regulated by TGF-β1 and was able to differentiate the sham and IRI even after the injured kidneys were recovered. Altogether, these data indicate that exo-miRs released in renal IRI are associated with TGF-β signaling. Temporal release of exo-miRs which share targets might be a regulatory mechanism to control the progression of AKI.
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U2 - 10.1038/s41598-019-40747-8
DO - 10.1038/s41598-019-40747-8
M3 - Article
C2 - 30886169
AN - SCOPUS:85063048087
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 4692
ER -