<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_1905-7415.1005.513_s_001_w2aab3b7b9b1b6b1aab1c17b1Aa"><h3>Background</h3><p>Chronic tubulointerstitial (TI) fibrosis is difficult to diagnose. Urinary exosomes contain many potential biomarkers, and may be useful to identify biomarkers of TI fibrosis. However, a suitable animal model to investigate urinary exosome biomarkers for TI fibrosis has not yet been specifically identified.</p></sec><sec id="j_1905-7415.1005.513_s_002_w2aab3b7b9b1b6b1aab1c17b2Aa"><h3>Objective</h3><p>To test the suitability of a folic-acid induced rat model of renal injury for identifying potential biomarkers of fibrosis from urinary exosomes.</p></sec><sec id="j_1905-7415.1005.513_s_003_w2aab3b7b9b1b6b1aab1c17b3Aa"><h3>Methods</h3><p>We employed a rat model of renal injury using a single intraperitoneal injection of folic acid. Urinary exosomes were isolated and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)</p></sec><sec id="j_1905-7415.1005.513_s_004_w2aab3b7b9b1b6b1aab1c17b4Aa"><h3>Results</h3><p>We demonstrated severe acute kidney injury after folic acid injection by a 6-fold decrease in creatinine clearance at day 2, severe inflammatory cell infiltration in the TI area at day 7, and renal fibrosis at day 14. We collected 24 h urine samples from folic acid-injected rats and vehicle-injected control rats at days 7 and 14, then isolated urinary exosomes using a differential centrifugation method. We found that levels of exosomal marker proteins ALG-2-interacting protein 1 (ALIX; PDCD6IP) and tumor susceptibility gene 101 (TSG101) were higher in folic acid-injected rats than in control rats. LC-MS/MS analysis of urinary exosomal proteins from the folic acid-injected and control rats identified 372 proteins, including various potential TI fibrosis biomarkers</p></sec><sec id="j_1905-7415.1005.513_s_005_w2aab3b7b9b1b6b1aab1c17b5Aa"><h3>Conclusion</h3><p>We demonstrated the feasibility of using a folic acid-induced rat model of TI fibrosis for urinary proteomic analysis. These rats excreted sufficient urinary exosomes permitting the large-scale analysis and discovery of potential biomarkers of renal fibrosis.</p></sec></abstract>

BackgroundChronic tubulointerstitial (TI) fibrosis is difficult to diagnose. Urinary exosomes contain many potential biomarkers, and may be useful to identify biomarkers of TI fibrosis. However, a suitable animal model to investigate urinary exosome biomarkers for TI fibrosis has not yet been specifically identified.ObjectiveTo test the suitability of a folic-acid induced rat model of renal injury for identifying potential biomarkers of fibrosis from urinary exosomes.MethodsWe employed a rat model of renal injury using a single intraperitoneal injection of folic acid. Urinary exosomes were isolated and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)ResultsWe demonstrated severe acute kidney injury after folic acid injection by a 6-fold decrease in creatinine clearance at day 2, severe inflammatory cell infiltration in the TI area at day 7, and renal fibrosis at day 14. We collected 24 h urine samples from folic acid-injected rats and vehicle-injected control rats at days 7 and 14, then isolated urinary exosomes using a differential centrifugation method. We found that levels of exosomal marker proteins ALG-2-interacting protein 1 (ALIX; PDCD6IP) and tumor susceptibility gene 101 (TSG101) were higher in folic acid-injected rats than in control rats. LC-MS/MS analysis of urinary exosomal proteins from the folic acid-injected and control rats identified 372 proteins, including various potential TI fibrosis biomarkersConclusionWe demonstrated the feasibility of using a folic acid-induced rat model of TI fibrosis for urinary proteomic analysis. These rats excreted sufficient urinary exosomes permitting the large-scale analysis and discovery of potential biomarkers of renal fibrosis.

A folic acid-induced rat model of renal injury to identify biomarkers of tubulointerstitial fibrosis from urinary exosomes

National Institute of Diabetes and Digestive and Kidney Diseases

Department of Microbiology, Faculty of Medicine

Asian Biomedicine

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

BackgroundChronic tubulointerstitial (TI) fibrosis is difficult to diagnose. Urinary exosomes contain many potential biomarkers, and may be useful to identify...

A folic acid-induced rat model of renal injury to identify biomarkers of tubulointerstitial fibrosis from urinary exosomes

Article Category: Technical report (Original)

Data publikacji: 31 mar 2017

Zakres stron: 491 - 502

DOI: https://doi.org/10.5372/1905-7415.1005.513

Słowa kluczowe
Biomarkers, chronic kidney disease, folic acid, interstitial fibrosis, proteomics, urine exosomes

© 2016 Panthip Rattanasinganchan, Kittipat Sopitthummakhun, Kent Doi, Xuzhen Hu, D. Michael Payne, Trairak Pisitkun, Asada Leelahavanichkul

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

A folic acid-induced rat model of renal injury to identify biomarkers of tubulointerstitial fibrosis from urinary exosomes

Article Category: Technical report (Original)

Data publikacji: 31 mar 2017

Zakres stron: 491 - 502

DOI: https://doi.org/10.5372/1905-7415.1005.513

Słowa kluczoweBiomarkers, chronic kidney disease, folic acid, interstitial fibrosis, proteomics, urine exosomes

© 2016 Panthip Rattanasinganchan, Kittipat Sopitthummakhun, Kent Doi, Xuzhen Hu, D. Michael Payne, Trairak Pisitkun, Asada Leelahavanichkul

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Słowa kluczowe
Biomarkers, chronic kidney disease, folic acid, interstitial fibrosis, proteomics, urine exosomes