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miR-1187 induces podocyte injury and diabetic nephropathy through autophagy
Abstract:
MicroRNAs plays important roles in the progression of diabetic nephropathy (DN) and podocyte injury. This study aimed to investigate the role and regulation mechanism of miR-1187 during the development of DN and podocyte injury. The content of miR-1187 in podocytes was up-regulated under high glucose (HG) treatment and increased in kidney tissue of db/db mice (DN model mice) compared with control db/m mice. The administration of miR-1187 inhibitor could decrease podocyte apoptosis induced by HG and attenuate the decline in renal function and reduce proteinuria as well as glomerular apoptosis in db/db mice. Mechanistically, miR-1187 could inhibit the autophagy level in HG-exposed podocytes and glomerulus of DN mice. Moreover, miR-1187 inhibitor could reduce HG-stimulated podocyte injury and autophagy flux inhibition. The mechanism may depend on autophagy. In conclusion, targeting miR-1187 may be a new therapeutic target for improving the high glucose damage of podocytes and the progression of DN.
Insights
MicroRNA-1187 (miR-1187) is elevated in diabetic nephropathy (DN) and promotes podocyte injury by inhibiting autophagy. Inhibiting miR-1187 may offer a new therapeutic strategy for DN.
Area of Science:
- Nephrology
- Molecular Biology
- Endocrinology
Background:
- Diabetic nephropathy (DN) is a major complication of diabetes, characterized by podocyte injury.
- MicroRNAs (miRNAs) are implicated in the pathogenesis of DN.
- The specific role of miR-1187 in DN and podocyte injury requires further investigation.
Purpose of the Study:
- To investigate the role and regulatory mechanism of miR-1187 in the development of DN and podocyte injury.
- To explore miR-1187 as a potential therapeutic target for DN.
Main Methods:
- Assessed miR-1187 expression in podocytes under high glucose (HG) conditions and in a mouse model of DN (db/db mice).
- Administered miR-1187 inhibitors to HG-treated podocytes and db/db mice.
- Evaluated podocyte apoptosis, renal function, proteinuria, and glomerular apoptosis.
- Investigated the effect of miR-1187 on autophagy levels and flux in podocytes and glomeruli.
Main Results:
- miR-1187 expression was upregulated in podocytes exposed to HG and in the kidneys of db/db mice.
- Inhibition of miR-1187 reduced HG-induced podocyte apoptosis, improved renal function, decreased proteinuria, and attenuated glomerular apoptosis in db/db mice.
- miR-1187 was found to inhibit autophagy in HG-exposed podocytes and glomeruli of DN mice.
- miR-1187 inhibition reversed HG-induced podocyte injury and autophagy flux inhibition.
Conclusions:
- miR-1187 plays a critical role in promoting podocyte injury and DN progression, partly by inhibiting autophagy.
- Targeting miR-1187 presents a potential therapeutic strategy for mitigating high glucose-induced podocyte damage and DN progression.
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