Banca de QUALIFICAÇÃO: IAGO DE SOUZA GOMES

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : IAGO DE SOUZA GOMES
DATE: 02/06/2023
TIME: 13:30
LOCAL: Link de acesso para videoconferência: https://meet.google.com/bse-qhhq-gpg
TITLE:
RENAL CORTEX PROTEINS AS DIABETIC NEPHROPATHY BIOMARKER

KEY WORDS:
Diabetic Kidney Disease; Extracellular Urinary Vesicles; Nephrin; Podocin and WT1.

PAGES: 50
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:
Diabetic Kidney Disease (DRD) is one of the complications resulting from Diabetes
mellitus (DM), and despite advances in the knowledge of its pathogenesis, the
mechanism that chronic hyperglycemia leads to kidney damage is not fully
understood. The loss of podocytes from the renal glomerulus is an early event in
the development of DRD and involves proteins and factors in maintaining the
integrity of the glomerular filtration slit such as nephrin, podocin and WT1. Thus,
the present study aimed to evaluate the expression of mRNAs of NPHS1
(nephrin), NPHS2 (podocin) and WT1 (Willms' Tumor 1) in the renal cortex, and
the expression of the respective proteins in the extracellular vesicles urinary tract
(VEUs). Twenty-three male Wistar rats were divided into 3 groups and followed for
60 days: control (C), streptozotocin-induced diabetics (D) and streptozotocin
induced diabetics treated with insulin (DT). Serum (glucose, urea, creatinine, total
proteins and albumin) and urinary (urinary albumin-to-creatinine ratio (ACR))
biochemical parameters were evaluated. Nphs1, Nphs2 and Wt1 mRNA
expression by RT-qPCR and protein expression by Western blot were performed
in tissue samples from the renal cortex. After a period of 60 days, the results for
biochemical parameters revealed that insulin promoted glycemic control, with a
significant reduction in glycemia (p < 0.001). For the renal profile, the significant
reduction in ACR for the group treated with insulin in relation to the diabetic group
(p= 0.036) stands out, although with values still significantly increased in relation to
the control group (p = 0.034). For the expression of mRNA (Nphs1, Nphs2 and
Wt1) and proteins (Nephrin, Podocina and WT1), in the renal tissue and in the
VEUs, the results show, for the diabetic group, a significant increase of mRNA
expression in the renal tissue for Nphs1, Nphs2 and Wt1 (p= 0.001, for all groups),
as well as a decrease in the expression of nephrin, podocin and WT1 proteins in
the renal tissue (p = 0.021, 0.006 and 0.004, respectively) and an increase in the
expression of proteins in the urinary vesicles (p=0.034, 0.014 and 0.004,
respectively). For the diabetic group treated with insulin, a significant increase in
mRNA expression for Nphs1, Nphs2 and Wt1 was observed for the renal tissue in
relation to the control group, although approximately 2x, 4x and 12x lower,
respectively, when compared to the group untreated diabetes compared to the
control group. Regarding the expression of nephrin, podocin and WT1 proteins, there was a significant reduction in the renal tissue (p values = 0.021, 0.006 and
0.004, respectively) for the diabetic group when compared to the control group, but
about 4x, 2x and 4x lower , respectively, for the insulin-treated group when
compared to the untreated diabetic group compared to the control group. As for
the urinary vesicles, a significant increase in the expression of the proteins
nephrin, podocin and WT1 was observed for the diabetic group (p values = 0.034,
0.014 and 0.004, respectively), but that for the diabetic group treated with insulin
the increase in expression was about 3x, 2x and 3x lower than those observed for
the diabetic group compared to the control group. These results suggest that the
hyperglycemic state characteristic of diabetes leads to a compensatory
mechanism with upregulation of mRNA expression of the Nphs1, Nphs2 and Wt1
genes in the renal tissue to maintain tissue integrity, but which is not sufficient in
view of the significant reduction in expression of the respective proteins in the
renal tissue and increased loss of the same in the VEUs, signaling the
development of diabetic kidney disease. However, treatment with insulin revealed
that with better glycemic control, renal alteration, although present, is milder.
Furthermore, it is important to highlight the representation of tissue and/or urinary
proteins, nephrin, podocin and WT1, as possible specific and sensitive markers in
the identification of the different stages of development of CKD.

COMMITTEE MEMBERS:
Externo ao Programa - 1667882 - BENTO JOAO DA GRACA AZEVEDO ABREU - nullPresidente - 1801992 - PAULA RENATA LIMA MACHADO
Externa à Instituição - RENATA CAROLINE COSTA DE FREITAS - HMS
Notícia cadastrada em: 17/05/2023 13:55
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