The effect of lncRNA-ARAP1-AS2/ARAP1 on high glucose-induced cytoskeleton rearrangement and epithelial-mesenchymal transition in human renal tubular epithelial cells

Area of Science:

• Molecular Biology
• Cell Biology
• Diabetology

Background:

• Epithelial-mesenchymal transition (EMT) is crucial in diabetic renal fibrosis.
• ARAP1 gene proximity to Type 2 diabetes risk alleles suggests a role in the disease.
• The specific functions of ARAP1 and its antisense RNA, ARAP1-AS2, in diabetes remain largely unknown.

Purpose of the Study:

• To investigate the expression changes of ARAP1 and ARAP1-AS2 under high glucose (HG) conditions.
• To elucidate the roles of ARAP1 and ARAP1-AS2 in the EMT process within renal cells.

Main Methods:

• HK-2 cells were cultured under high glucose conditions to assess transcript levels.
• ARAP1-AS2 overexpression and ARAP1 knockdown experiments were performed.
• Cdc42-GTP levels, cytoskeleton rearrangement, cell viability, migration, and fibrosis markers were analyzed.

Main Results:

• High glucose significantly upregulated ARAP1-AS2 and ARAP1 expression in HK-2 cells.
• ARAP1-AS2 overexpression enhanced EMT, while ARAP1 knockdown inhibited EMT and fibrosis markers.
• HG increased Cdc42-GTP, cytoskeleton rearrangement, cell viability, and migration, effects reversed by ARAP1 knockdown.

Conclusions:

• ARAP1-AS2 and ARAP1 are upregulated by high glucose in renal cells.
• The ARAP1-AS2/ARAP1 axis, via Cdc42-GTP, plays a significant role in promoting EMT and potentially diabetic renal fibrosis.