Brilliant blue G, a P2X7 receptor antagonist, attenuates early phase of renal inflammation, interstitial fibrosis and is associated with renal cell proliferation in ureteral obstruction in rats

Autor: Christina Maeda Takiya, Felipe M. Ornellas, Debora S. Ornellas, Marcelo M. Morales, José Monteiro Sad Pereira, Lucio R. Cardoso, André Luis Barreira, Luiz Carlos D. de Miranda, Alberto Schanaider, Maurilo Leite, Conrado Rodrigues Gomes, Robson Coutinho-Silva
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Nephrology
Male
Time Factors
Interleukin-1beta
Apoptosis
lcsh:RC870-923
urologic and male genital diseases
Kidney
0302 clinical medicine
Fibrosis
Cell Movement
Rosaniline Dyes
Myofibroblasts
Nephritis
Renal inflammation
Purinergic receptor
female genital diseases and pregnancy complications
Up-Regulation
medicine.anatomical_structure
Kidney Tubules
P2X7 receptor
medicine.symptom
Research Article
Ureteral Obstruction
Collagen Type IV
medicine.medical_specialty
Purinergic P2X Receptor Antagonists
Antigens
Differentiation
Myelomonocytic
Inflammation
Collagen Type I
Transforming Growth Factor beta1
03 medical and health sciences
Downregulation and upregulation
Antigens
CD
Internal medicine
medicine
Animals
RNA
Messenger
Rats
Wistar
HSP47 Heat-Shock Proteins
Cell Proliferation
business.industry
Cell growth
urogenital system
Macrophages
medicine.disease
lcsh:Diseases of the genitourinary system. Urology
Actins
Rats
030104 developmental biology
Endocrinology
Collagen Type III
Unilateral ureteral obstruction
business
030217 neurology & neurosurgery
Zdroj: BMC Nephrology
BMC Nephrology, Vol 21, Iss 1, Pp 1-11 (2020)
ISSN: 1471-2369
Popis: Background Previous study showed that purinergic P2X7 receptors (P2X7R) reach the highest expression in the first week after unilateral ureteral obstruction (UUO) in mice, and are involved in the process of inflammation, apoptosis and fibrosis of renal tissue. We, herein, document the role of purinergic P2X7 receptors activation on the third day of UUO, as assessed by means of BBG as its selective inhibitor. Methods We investigated the effects of brilliant blue G (BBG), a P2X7R antagonist, in the third day of kidney tissue response to UUO in rats. For this purpose, male Wistar rats submitted to UUO or sham operated, received BBG or vehicle (V), comprising four groups: UUO-BBG, UUO-V, sham-BBG and sham-V. The kidneys were harvested on day 3 UUO and prepared for histology, immunohistochemistry (P2X7R, PCNA, CD-68, α-sma, TGF-β1, Heat-shock protein-47, TUNEL assay), quantitative real-time PCR (IL-1β, procollagens type I, III, and IV) for mRNA quantification. Results The group UUO-V presented an enhancement in tubular cell P2X7-R expression, increase influx of macrophages and myofibroblasts, HSP-47 and TGF- β1 expression. Also, upregulation of procollagen types I, III, and IV, and IL-1β mRNAs were seen. On the other hand, group UUO-BBG showed lower expression of procollagens and IL-1β mRNAs, as well as less immunoreactivity of HSP-47, TGF-β, macrophages, myofibroblasts, and tubular apoptosis. This group also presented increased epithelial cell proliferation. Conclusion BBG, a known highly selective inhibitor of P2X7R, attenuated renal inflammation, collagen synthesis, renal cell apoptosis, and enhanced renal cell proliferation in the early phase of rat model of UUO.
Databáze: OpenAIRE
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