PMID- 34466631
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220426
IS  - 2352-3204 (Electronic)
IS  - 2352-3204 (Linking)
VI  - 18
DP  - 2021 Dec
TI  - The protective mechanism of Klotho gene-modified bone marrow mesenchymal stem 
      cells on acute kidney injury induced by rhabdomyolysis.
PG  - 255-267
LID - 10.1016/j.reth.2021.07.003 [doi]
AB  - BACKGROUND: Studies have shown that the Klotho gene has tremendous potential for 
      future therapeutic purposes in both acute and chronic kidney diseases (CKD). This 
      study aimed to investigate the possible protective mechanisms of the Klotho gene 
      against acute kidney injury (AKI) induced by rhabdomyolysis (RM). METHODS: In 
      this study, bone marrow mesenchymal stem cells (BMSCs) were transfected with 
      recombinant adenoviruses expressing the Klotho gene (BMSCs-Klotho) and by those 
      expressing empty vector (BMSCs-EV). After successful transfection, we tested the 
      proliferation, secretion and migration abilities of the BMSCs-Klotho compared 
      with those of the BMSCs-EV and BMSCs. Then, 30 male C57BL/6 mice were examined, 
      with 6 mice randomly assigned to the control group (PBS injected into the tail 
      vein, CON) or one of the four treatment groups treated with either BMSCs-Klotho 
      (AKI+BMSCs-Klotho), BMSCs-EV (AKI+BMSCs-EV), BMSCs (AKI+BMSCs) or PBS (AKI+PBS) 
      after induction of RM. Seventy-two h after treatment, serum creatinine (SCr) and 
      blood urea nitrogen (BUN) levels were obtained to assess renal function, and 
      renal tissue was obtained to measure kidney tissue damage. Additionally, kidney 
      protective mechanism-related indexes, such as EPO, IGF-1, KIM-1 and HIF-1, were 
      analysed using Western blot analysis and immunohistochemistry. RESULTS: The 
      results obtained showed that the proliferation, secretory and migration abilities 
      of the BMSCs were significantly increased after transfection with the Klotho 
      gene. Treatment with BMSCs-Klotho, BMSCs-EV or BMSCs improved renal function 
      compared to treatment with PBS. However, the improvement observed in renal 
      function in the BMSCs-Klotho group was better than that of the other groups. 
      Histological analysis demonstrated that tissue damage was significantly decreased 
      in the mice in the AKI+BMSCs-Klotho, AKI+BMSCs-EV or AKI+BMSCs groups compared to 
      that in the mice in the AKI+PBS group. However, the best recovery was observed in 
      the mice treated with BMSCs-Klotho concomitantly. Furthermore, the expression of 
      protective factors erythropoietin (EPO) and insulin-like growth factor 1 (IGF-1) 
      increased obviously, and the injury biomarkers kidney injury molecule 1 (KIM-1) 
      and hypoxia inducible factor 1 (HIF-1) decreased notably in the group of 
      BMSCs-Klotho, BMSCs-EV and BMSCs. Additionally, the levels of the aforementioned 
      protein indicators in the AKI+BMSCs-Klotho group were not different from those in 
      the CON group. CONCLUSION: Klotho overexpression exerted positive effects on 
      BMSCs and markedly promoted recovery from RM-induced AKI. These findings suggest 
      that the overexpression of the Klotho gene might be a good candidate for further 
      therapy for AKI in clinical trials.
CI  - (c) 2021 The Japanese Society for Regenerative Medicine. Production and hosting by 
      Elsevier B.V.
FAU - Ni, WenHui
AU  - Ni W
AD  - Department of Renal Medicine, First People's Hospital of Zhangjiagang City, 
      China.
FAU - Zhang, Ying
AU  - Zhang Y
AD  - Department of Renal Medicine, Xuzhou Medical University Affiliated Hospital, 
      China.
FAU - Yin, Zhongcheng
AU  - Yin Z
AD  - Department of Renal Medicine, Xuzhou Medical University Affiliated Hospital, 
      China.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210813
PL  - Netherlands
TA  - Regen Ther
JT  - Regenerative therapy
JID - 101709085
PMC - PMC8367782
OTO - NOTNLM
OT  - AKI
OT  - BMSCs
OT  - EPO
OT  - HIF-1
OT  - IGF-1
OT  - KIM-1
OT  - Klotho
OT  - Renal function
OT  - Tissue damage
COIS- The authors declared that they have no conflicts of interest to this work. We 
      declare that we do not have any commercial or associative interest that 
      represents a conflict of interest in connection with the work submitted.
EDAT- 2021/09/02 06:00
MHDA- 2021/09/02 06:01
PMCR- 2021/08/13
CRDT- 2021/09/01 07:26
PHST- 2021/04/25 00:00 [received]
PHST- 2021/06/21 00:00 [revised]
PHST- 2021/07/13 00:00 [accepted]
PHST- 2021/09/01 07:26 [entrez]
PHST- 2021/09/02 06:00 [pubmed]
PHST- 2021/09/02 06:01 [medline]
PHST- 2021/08/13 00:00 [pmc-release]
AID - S2352-3204(21)00056-0 [pii]
AID - 10.1016/j.reth.2021.07.003 [doi]
PST - epublish
SO  - Regen Ther. 2021 Aug 13;18:255-267. doi: 10.1016/j.reth.2021.07.003. eCollection 
      2021 Dec.