|
KMID : 1037120220400040580
|
|
The World Journal of Men′s Health
2022 Volume.40 No. 4 p.580 ~ p.599
|
|
|
Heat Shock Protein 70 in Penile Neurovascular Regeneration Requires Cystathionine Gamma-Lyase
|
|
Ghatak Kalyan
Yin Guo Nan
Hong Soon-Sun
Kang Ju-Hee
Suh Jun-Kyu
Ryu Ji-Kan
|
|
|
Abstract
|
|
|
Purpose: Diabetes mellitus, one of the major causes of erectile dysfunction, leads to a poor response to phosphodiesterase-5 inhibitors. Heat shock protein 70 (Hsp70), a ubiquitous molecular chaperone, is known to play a role in cell survival and neuroprotection. Here, we aimed to assess whether and how Hsp70 improves erectile function in diabetic mice.
Materials and Methods: Eight-week-old male C57BL/6 mice and Hsp70-Tg mice were used in this study. We injected Hsp70 protein into the penis of streptozotocin (STZ)-induced diabetic mice. Detailed mechanisms were evaluated in WT or Hsp70-Tg mice under normal and diabetic conditions. Primary MCECs, and MPG and DRG tissues were cultivated under normal-glucose and high-glucose conditions.
Results: Using Hsp70-Tg mice or Hsp70 protein administration, we demonstrate that elevated levels of Hsp70 restores erectile function in diabetic mice. We found that cystathionine gamma-lyase (Cse) is a novel target of Hsp70 in this process, showing that Hsp70-Cse acts through the SDF1/HO-1/PI3K/Akt/eNOS/NF-κB p65 pathway to exert its neurovascular regeneration-promoting effects. Coimmunoprecipitation and pull-down assays using mouse cavernous endothelial cells treated with Hsp70 demonstrated physical interactions between Hsp70 and Cse with a dissociation constant of 1.8 nmol/L.
Conclusions: Our findings provide novel and solid evidence that Hsp70 acts through a Cse-dependent mechanism to mediate neurovascular regeneration and restoration of erectile function under diabetic conditions.
|
|
|
KEYWORD
|
|
|
Cystathionine gamma-lyase, Diabetes mellitus, Erectile dysfunction, Heat shock protein 70, Neovascularization, Nerve regeneration
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
   
|