Bone Marrow Derived Mesenchymal Stromal Cells Ameliorate Ischemia/Reperfusion Injury-Induced Acute Kidney Injury in Rats Via Secreting Tumor Necrosis Factor-Inducible Gene 6 Protein

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2019 Apr 16

PMID 30984789

Citations 11

Authors

Yue Chen

XiaoChen Tang

Ping Li

Ying Zhou

Ting Xue

Jie Liu

Chen Yu

Affiliations

Soon will be listed here.

Abstract

Aims: To investigate whether bone marrow derived mesenchymal stromal cells (BMSC) have ameliorated ischemia/reperfusion injury-induced acute kidney injury (IRI-AKI) via tumor necrosis factor-inducible gene 6 protein (TSG-6) and how TSG-6 exerted this effect.

Methods: We used lentiviral vectors of short hairpin RNA (shRNA) targeting TSG-6 gene to silence TSG-6 in BMSC. And TSG-6-silenced BMSC were administrated into IRI-AKI rats. Then we analyzed serum creatinine (Scr) and renal histology of IRI-AKI rats treated with BMSC after different pretreatments. Furthermore, we explored the effect of TSG-6 on renal tubular epithelial cells proliferation and assays.

Results: The Scr levels of IRI-AKI rats treated with BMSC (73.5±7.8 mol/L) significantly decreased compared to those of IRI-AKI rats treated without BMSC (392.5±24.8 mol/L, P<0.05) or with DMEM (314.0±19.8 mol/L, P<0.05). Meanwhile, the renal tissue injury in IRI-AKI rats treated with BMSC improved markedly. However, the Scr levels of IRI-AKI rats treated with TSG-6-silenced BMSC (265.1±21.2 mol/L) significantly increased compared to those with BMSC (74.0±8.5 mol/L, P<0.05). The proportion of Ki67-positive cells was reduced in IRI-AKI rats treated with TSG-6-silenced BMSC compared to that in IRI-AKI rats treated with BMSC (29.7±0.8% versus 43.4±3.0%, P<0.05). , the cell proliferation rate of TSG-6-stimulated NRK-52E cells under hypoxia (89.2±3.9%) increased significantly compared to that of NRK-52E cells alone under hypoxia (82.4±0.8%, P<0.05). Similarly, the proportion of Ki67-positive cells was significantly elevated in TSG-6-stimulated NRK-52E cells under hypoxia. Furthermore, TSG-6 could inhibit infiltration of neutrophils in kidney tissue of IRI-AKI.

Conclusions: TSG-6 plays a key role in the treatment of IRI-AKI with BMSC, which may be due to its effect on promoting renal tubular epithelial cells proliferation by modulating inflammation.

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