Related Experiment Video
Updated: Aug 5, 2026
Cavernous Nerve Stimulation and Recording of Intracavernous Pressure in a Rat
Published on: April 23, 2018
Upregulation of the Nestin/NRF2/PRDX2 Signaling Pathway in Penile Tissues Ameliorates Erectile Function in Rats with
Jian Zhou1,2, Jun Jiang3, Rui Jiang4
1Department of Urology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Purpose:
Cavernous nerve injury (CNI) is a major cause of erectile dysfunction (ED), and oxidative stress plays a key role in the underlying molecular mechanisms. Nestin contributes to the maintenance of intracellular redox balance. However, whether CNI affects erectile function in rats via the Nestin-related pathway is unclear.
Materials And Methods:
The GSE31247 dataset and a knowledge-guided gene selection approach were analyzed to identify key differentially expressed Nestin genes in cavernous tissue between CNI and Sham-operated rats. The effect of the Nestin, NRF2, and PRDX2 pathways on oxidative stress and pyroptosis-related markers was evaluated in PC-12 cells. In vivo, Nestin expression was examined in the corpus cavernosum of rats with bilateral CNI (BCNI). The effects of upregulated Nestin expression and icariin treatment on erectile function, as well as the underlying mechanisms, were evaluated.
Results:
Nestin was significantly downregulated in the CNI group versus the Sham group, thus indicating its potential involvement in neuropeptide hormone activity and neurotransmitter transport/signaling pathways. Icariin upregulates the expression of Nestin, NRF2, and PRDX2 in PC-12 cells, suppresses oxidative stress and pyroptosis markers, and increases nNOS expression. Conversely, Prdx2 knockdown in PC-12 cells increased oxidative stress and pyroptosis-related markers while decreasing nNOS (p<0.05). Compared to the Sham group, the BCNI group showed lower Nestin, NRF2, and PRDX2 levels and a reduced ICPmax/MAP ratio (p<0.05). Nestin upregulation or icariin treatment in BCNI rats enhanced NRF2/PRDX2 expression, inhibited oxidative stress and pyroptosis-related markers, and increased nNOS, eNOS and the ICPmax/MAP ratio (p<0.05).
Conclusions:
Nestin downregulation in the penile tissue of BCNI rats inhibits NRF2 and PRDX2 expression, contributing to ED. Nestin gene transfection or icariin treatment in the corpus cavernosum upregulates Nestin, NRF2, and PRDX2 pathway proteins, reduces oxidative stress and pyroptosis-related markers, increases nNOS and eNOS, and ultimately improves erectile function in BCNI rats.
