PMID- 34517258 OWN - NLM STAT- MEDLINE DCOM- 20220214 LR - 20220214 IS - 1618-0372 (Electronic) IS - 0065-1281 (Linking) VI - 123 IP - 7 DP - 2021 Oct TI - Protective action of ultrasound-guided intraparenchymal transplantation of BMSCs in adriamycin nephropathy rats through the RIPK3/MLKL and NLRP3 pathways. PG - 151773 LID - S0065-1281(21)00095-7 [pii] LID - 10.1016/j.acthis.2021.151773 [doi] AB - BACKGROUND: Bone marrow stromal cells (BMSCs) are an effective new strategy for the treatment of kidney diseases. At present, noninvasive and efficient transplantation approaches to homing BMSCs to the renal parenchyma is still a serious challenge. The aim of this study was to investigate the feasibility and potential mechanism of ultrasound-guided intraparenchymal transplantation of BMSCs for the treatment of adriamycin nephropathy (AN) in rats. MATERIALS AND METHODS: A rat AN model was induced by 2 injections of doxorubicin. The rats were randomly divided into 4 groups (n = 10 animals in each group) : normal group (N group, no treatment), control medium group (CM group, transplant medium 1.0 mL), adriamycin nephropathy group (ADR group, phosphate buffered saline 1.0 mL), or BMSCs group (BMSCs fluid 1.0 mL). Intraparenchymal injection was completed under ultrasound guidance. After 4 weeks of treatment, blood samples were collected for serum biochemical measurements and ELISAs. The kidneys were removed for histopathological examination, electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), and western blot analysis. RESULTS: No deaths occurred in any group after BMSCs transplantation through the renal parenchyma under ultrasound guidance. Compared with the N and CM groups, in the ADR group, blood serum creatinine (SCr), blood urea nitrogen (BUN) and urine albumin (ALb) were higher, glomerular and tubular dilatation was observed, the number of apoptotic cells was higher, and the protein levels of receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like protein (MLKL) and nucleotide leukin-rich polypeptide 3 (NLRP3), key components of pathways in rat kidney, were significantly higher. Compared with those in the ADR group, the levels of SCr, BUN, ALb and serum proinflammatory cytokines in the BMSCs group were lower, the pathological structure of the kidney was improved, the number of apoptotic cells was lower, and the levels of RIPK3/MLKL and NLRP3 were significantly lower. CONCLUSION: Ultrasound-guided intraparenchymal transplantation of BMSCs regulated the RIPK3/MLKL and NLRP3 pathways in a minimally invasive and safe manner, thereby inhibiting renal necrosis and inflammation and playing a protective role in rat AN. CI - Copyright (c) 2021 Elsevier GmbH. All rights reserved. FAU - Xia, Chunjuan AU - Xia C AD - Department of Ultrasound, The Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China. FAU - Shao, Lishi AU - Shao L AD - Department of Radiology, the Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China. FAU - Ma, Yiqun AU - Ma Y AD - Department of Radiology, the Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China. FAU - Wang, Xinghong AU - Wang X AD - Department of Hepatobiliary Surgery, Kunming Medical University, Yunnan, 650500, China. FAU - Zhang, Ya AU - Zhang Y AD - Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan, 650500, China. FAU - Shi, Cheng AU - Shi C AD - Department of Radiology, the Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China. FAU - Li, Jiaqi AU - Li J AD - Department of Radiology, the Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China. FAU - Zhang, Weihu AU - Zhang W AD - Department of Radiology, the Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China. FAU - Li, Hongjun AU - Li H AD - Institute of Medical Biology Chinese Academy of Medical Sciences, Yunnan, 650101, China. FAU - Wang, Jiaping AU - Wang J AD - Department of Radiology, the Second Affiliated Hospital of Kunming Medical University, Yunnan, 650101, China. Electronic address: jiapingwang12@163.com. LA - eng PT - Journal Article DEP - 20210910 PL - Germany TA - Acta Histochem JT - Acta histochemica JID - 0370320 RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, rat) RN - 80168379AG (Doxorubicin) RN - EC 2.7.- (MLKL protein, rat) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases) SB - IM EIN - Acta Histochem. 2022 Feb;124(2):151846. PMID: 35033378 MH - Animals MH - Bone Marrow Cells/*metabolism MH - Doxorubicin/*adverse effects/pharmacology MH - *Kidney Diseases/chemically induced/metabolism/therapy MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism MH - Protein Kinases/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptor-Interacting Protein Serine-Threonine Kinases/*metabolism MH - *Signal Transduction OTO - NOTNLM OT - Adriamycin nephropathy OT - Bone marrow stromal cells OT - NLRP3 OT - RIPK3/MLKL OT - Transplantation OT - Ultrasound guidance EDAT- 2021/09/14 06:00 MHDA- 2022/02/15 06:00 CRDT- 2021/09/13 20:34 PHST- 2021/05/24 00:00 [received] PHST- 2021/08/09 00:00 [revised] PHST- 2021/08/17 00:00 [accepted] PHST- 2021/09/14 06:00 [pubmed] PHST- 2022/02/15 06:00 [medline] PHST- 2021/09/13 20:34 [entrez] AID - S0065-1281(21)00095-7 [pii] AID - 10.1016/j.acthis.2021.151773 [doi] PST - ppublish SO - Acta Histochem. 2021 Oct;123(7):151773. doi: 10.1016/j.acthis.2021.151773. Epub 2021 Sep 10.