Bone marrow mononuclear cells shift bioactive lipid pattern in injured kidney towards tissue repair in rats with unilateral ureteral obstruction.
BACKGROUND
Bioactive lipids are important in tissue injury and regeneration. Ceramide (Cer) is known for its pro-apoptotic action and sphingosine-1-phosphate (S1P) for inducing proliferation and cell survival; diacylglycerol (DAG) and lysophosphatidic acid (LPA) are involved in various signalling pathways including modulation of ion transport. LPA signalling through its receptor LPA(1) is also related to the progression of fibrosis. This study investigated the modulation of lipid signalling pathways induced by administration of bone marrow-derived mononuclear cells (BMMC) in chronic kidney disease.


METHODS
Unilateral ureteral obstruction (UUO) was followed by intravenous injection of ∼2 × 10(7) BMMC. Controls were UUO group treated with buffered solution and sham-operated group. Animals were killed 14 days after surgery, and lipid phosphorylation assays and immunoblotting were performed on the kidney homogenates.


RESULTS
More DAG was available in the UUO rats (2.4 ± 0.4 and 2.4 ± 0.3 vs 1.0 ± 0.2 pmol (32)PA mg(-)(1) min(-)(1), in UUO and UUO + BMMC vs SHAM). Sphingosine kinase was 150 ± 12% more active in UUO + BMMC than in UUO and SHAM. Cer levels were 76 ± 7% lower in the UUO + BMMC than UUO. LPA receptor type 1 (LPA(1)) expression was 169 ± 7% higher in the UUO group than in UUO + BMMC and SHAM. BMMC maintain control levels of Ca(2+)-ATPase expression altered by UUO by 40%.


CONCLUSIONS
BMMC infusion modulated diverse lipid signalling pathways and protein expression, shifted sphingolipid metabolism toward a regenerative pattern and favourably reduced the levels of a receptor involved in the progression of tissue fibrosis. These results strengthen the benefits of BMMC treatment and give insight into its paracrine mechanisms of action.
Verdoorn
Karine S
KS
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Lindoso
Rafael S
RS
Lowe
Jennifer
J
Lara
Lucienne S
LS
Vieyra
Adalberto
A
Einicker-Lamas
Marcelo
M
D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D016026:Bone Marrow Transplantation; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D004075:Diglycerides / Q000378:metabolism; D007668:Kidney / Q000473:pathology / Q000502:physiology*; D008055:Lipids / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013107:Sphingolipids / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
D004075:Diglycerides; D008055:Lipids; D049368:Receptors, Lysophosphatidic Acid; D013107:Sphingolipids; D000252:Calcium-Transporting ATPases