Lipin1 Alleviates Autophagy Disorder in Sciatic Nerve and Improves Diabetic Peripheral Neuropathy.

Abstract

Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes, and its neural mechanisms underlying the pathogenesis remain unclear. Autophagy plays an important role in neurodegenerative diseases and nerve tissue injury. Lipin1 is a phosphatidic acid phosphatase enzyme that converts phosphatidic acid (PA) into diacylglycerol (DAG), a precursor of triacylglycerol and phospholipids which plays an important role in maintaining normal peripheral nerve conduction function. However, whether Lipin1 involved in the pathogenesis of DPN via regulation of autophagy is not elucidated. Here, we show that the Lipin1 expression was downregulated in streptozotocin (STZ)-induced DPN rat model. Interestingly, STZ prevented DAG synthesis, and resulted in autophagic hyperactivity, effects which may increase the apoptosis of Schwann cells and lead to demyelination in sciatic nerve in DPN rats. More importantly, upregulation of lipin1 in the DPN rats ameliorated autophagy disorders and pathological changes of the sciatic nerve, which associated with the increase of the motor nerve conductive velocity (MNCV) in DPN rats. In contrast, knockdown of lipin1 exacerbates neuronal abnormalities and facilitates the genesis of DPN phenotypes in rats. In addition, overexpression of lipin1 in RSC96 cells also significantly decreased the autophagic hyperactivity and apoptosis induced by hyperglycemia. These results suggest that lipin1 may exert neuroprotection within the sciatic nerve anomalies and may serve as a potential therapeutic target for the treatment of DPN.

• Authors: Meijian Wang, Min Xie, Shuyan Yu, Pan Shang, Cong Zhang, Xiaolin Han, Cuiqin Fan, Li Chen, Xianghua Zhuang, Shihong Chen
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 58 Issue 11 Pg. 6049-6061 (Nov 2021) ISSN: 1559-1182 [Electronic] United States
• PMID: 34435332 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Diglycerides
• Lpin1 protein, rat
• Nuclear Proteins
• Recombinant Proteins

Topics

• Animals
• Apoptosis
• Autophagy (physiology)
• Cells, Cultured
• Demyelinating Diseases (etiology, physiopathology, therapy)
• Diabetes Mellitus, Experimental (blood, complications)
• Diabetic Neuropathies (physiopathology)
• Diglycerides (biosynthesis)
• Down-Regulation
• Gene Knockdown Techniques
• Genetic Vectors (therapeutic use)
• Hyperalgesia (etiology, therapy)
• Hyperglycemia (etiology, metabolism)
• Male
• Nerve Degeneration (etiology, physiopathology)
• Neural Conduction
• Nuclear Proteins (biosynthesis, genetics, physiology, therapeutic use)
• Rats
• Rats, Wistar
• Recombinant Proteins (metabolism)
• Schwann Cells (metabolism)
• Sciatic Nerve (physiopathology)