Abstract
Mesenchymal stem cells (MSCs) have regenerative properties in acute kidney injury (AKI). However, the potential function of MSCs in chronic kidney disease remains elusive. Renal fibrosis is the common endpoint of chronic progressive kidney diseases and causes a considerable health burden worldwide. In this study, the protective effects of bone marrow mesenchymal stem cells (BM-MSCs) were assessed in repeated administration of low-dose cisplatin-induced renal fibrosis mouse model in vivo as well as a TGF-β1-induced fibrotic model in vitro. Differentially expressed miRNAs in mouse renal tubular epithelial cells (mRTECs) regulated by BM-MSCs were screened by high-throughput sequencing. We found microRNA (miR)-146a-5p was the most significant up-regulated miRNA in mRTECs. In addition, the gene Tfdp2 was identified as one target gene of miR-146a-5p by bioinformatics analysis. The expression of Tfdp2 in the treatment of BM-MSCs on cisplatin-induced renal injury was evaluated by immunohistochemistry analysis. Our results indicate that BM-MSC attenuates cisplatin-induced renal fibrosis by regulating the miR-146a-5p/Tfdp2 axis in mRTECs.
Highlights
Renal fibrosis is characterized by the activation of massive fibroblast and deposition of the fibrotic matrix in kidney tissue, which is considered as the common endpoint of chronic kidney disease (CKD) [1, 2]
There was no significant difference in the appearance of the kidney between cisplatin group and cisplatin +BM-Mesenchymal stem cells (MSCs) group (Figure 1B)
Analysis of fibrotic gene markers by RT-qPCR showed that the transcript levels of a-SMA and Col1a1 were significantly elevated in the cisplatin group compared to normal control group (NC) kidney tissues, while injection of bone marrow mesenchymal stem cells (BM-MSCs) reduced the levels of a-SMA and Col1a1 (Figures 1F, G)
Summary
Renal fibrosis is characterized by the activation of massive fibroblast and deposition of the fibrotic matrix in kidney tissue, which is considered as the common endpoint of chronic kidney disease (CKD) [1, 2]. Renal fibrosis mainly affects over 70-years old adults who account for over 10% of the world population [3]. In 2017, the global population of CKDs was about 6.97 million, and patients with CKD in China were approximately 1.32 million. Between 1990 and 2017, the global prevalence of CKD increased by 29.3%, and the global mortality rate increased by 41.5% [4]. The therapeutic strategies for CKD, such as kidney transplantation or dialysis, are still limited. A shortage of donor organs impedes kidney transplantation, and the cost of dialysis becomes
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