TY - JOUR
T1 - Inflammation- and cancer-related microRNAs in rat renal cortex after subchronic exposure to fluoride
AU - Parada-Cruz, Benjamín
AU - Aztatzi-Aguilar, Octavio Gamaliel
AU - Ramírez-Martínez, Gustavo
AU - Jacobo-Estrada, Tania Libertad
AU - Cárdenas-González, Mariana
AU - Escamilla-Rivera, Vicente
AU - Martínez-Olivas, Martha Adriana
AU - Narváez-Morales, Juana
AU - Ávila-Rojas, Sabino Hazael
AU - Álvarez-Salas, Luis Marat
AU - Barbier, Olivier
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - The proximal tubule is a target of subchronic exposure to fluoride (F) in the kidney. Early markers are used to classify kidney damage, stage, and prognosis. MicroRNAs (miRNAs) are small sequences of non-coding single-stranded RNA that regulate gene expression and play an essential role in developing many pathologies, including renal diseases. This study aimed to evaluate the expression of Cytokine-Chemokine molecules (IL-1α/1β/4/6/10, INF-γ, MIP-1α, MCP-1, RANTES, and TGF β1/2/3) and inflammation-related miRNAs to evidence the possible renal mechanisms involved in subchronic exposure to F. Total protein and miRNAs were obtained from the renal cortex of male Wistar rats exposed to 0, 15 and 50 mg NaF/L through drinking water during 40 and 80 days. In addition, cytokines-chemokines were analyzed by multiplexing assay, and a panel of 77 sequences of inflammatory-related miRNAs was analyzed by qPCR. The results show that cytokines-chemokines expression was concentration- and time-dependent with F, where the 50 mg NaF/L were the main altered groups. The miRNAs expression resulted in statistically significant differences in thirty-four miRNAs in the 50 mg NaF/L groups at 40 and 80 days. Furthermore, a molecular interaction network analysis was performed. The relevant pathways modified by subchronic exposure to fluoride were related to extracellular matrix-receptor interaction, Mucin type O-glycan biosynthesis, Gap junction, and miRNAs involved with renal cell carcinoma. Thus, F-induced cytokines-chemokines suggest subchronic inflammation; detecting miRNAs related to cancer and proliferation indicates a transition from renal epithelium to pathologic tissue after fluoride exposure.
AB - The proximal tubule is a target of subchronic exposure to fluoride (F) in the kidney. Early markers are used to classify kidney damage, stage, and prognosis. MicroRNAs (miRNAs) are small sequences of non-coding single-stranded RNA that regulate gene expression and play an essential role in developing many pathologies, including renal diseases. This study aimed to evaluate the expression of Cytokine-Chemokine molecules (IL-1α/1β/4/6/10, INF-γ, MIP-1α, MCP-1, RANTES, and TGF β1/2/3) and inflammation-related miRNAs to evidence the possible renal mechanisms involved in subchronic exposure to F. Total protein and miRNAs were obtained from the renal cortex of male Wistar rats exposed to 0, 15 and 50 mg NaF/L through drinking water during 40 and 80 days. In addition, cytokines-chemokines were analyzed by multiplexing assay, and a panel of 77 sequences of inflammatory-related miRNAs was analyzed by qPCR. The results show that cytokines-chemokines expression was concentration- and time-dependent with F, where the 50 mg NaF/L were the main altered groups. The miRNAs expression resulted in statistically significant differences in thirty-four miRNAs in the 50 mg NaF/L groups at 40 and 80 days. Furthermore, a molecular interaction network analysis was performed. The relevant pathways modified by subchronic exposure to fluoride were related to extracellular matrix-receptor interaction, Mucin type O-glycan biosynthesis, Gap junction, and miRNAs involved with renal cell carcinoma. Thus, F-induced cytokines-chemokines suggest subchronic inflammation; detecting miRNAs related to cancer and proliferation indicates a transition from renal epithelium to pathologic tissue after fluoride exposure.
KW - Cytokines
KW - Fluoride
KW - Kidney
KW - MiRNAs
KW - Renal cancer
KW - TGF-β
UR - http://www.scopus.com/inward/record.url?scp=85153936034&partnerID=8YFLogxK
U2 - 10.1016/j.cbi.2023.110519
DO - 10.1016/j.cbi.2023.110519
M3 - Artículo
C2 - 37121298
AN - SCOPUS:85153936034
SN - 0009-2797
VL - 379
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
M1 - 110519
ER -