Protective action of ultrasound-guided intraparenchymal transplantation of BMSCs in adriamycin nephropathy rats through the RIPK3/MLKL and NLRP3 pathways

Copyright © 2021 Elsevier GmbH. All rights reserved..

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.

Errataetall:

ErratumIn: Acta Histochem. 2022 Feb;124(2):151846. - PMID 35033378

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:123

Enthalten in:

Acta histochemica - 123(2021), 7 vom: 09. Okt., Seite 151773

Sprache:

Englisch

Beteiligte Personen:

Xia, Chunjuan [VerfasserIn]
Shao, Lishi [VerfasserIn]
Ma, Yiqun [VerfasserIn]
Wang, Xinghong [VerfasserIn]
Zhang, Ya [VerfasserIn]
Shi, Cheng [VerfasserIn]
Li, Jiaqi [VerfasserIn]
Zhang, Weihu [VerfasserIn]
Li, Hongjun [VerfasserIn]
Wang, Jiaping [VerfasserIn]

Links:

Volltext

Themen:

80168379AG
Adriamycin nephropathy
Bone marrow stromal cells
Doxorubicin
EC 2.7.-
EC 2.7.11.1
Journal Article
MLKL protein, rat
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3
Nlrp3 protein, rat
Protein Kinases
RIPK3/MLKL
Receptor-Interacting Protein Serine-Threonine Kinases
Transplantation
Ultrasound guidance

Anmerkungen:

Date Completed 14.02.2022

Date Revised 14.02.2022

published: Print-Electronic

ErratumIn: Acta Histochem. 2022 Feb;124(2):151846. - PMID 35033378

Citation Status MEDLINE

doi:

10.1016/j.acthis.2021.151773

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM330594079