wawasan - Computational Biology - # Cellular Mechanisms of Diabetic Erectile Dysfunction

Single-Cell Transcriptome Analysis Reveals Pericyte Dysfunction as a Key Driver of Diabetic Erectile Dysfunction

Q: How do the identified LBH-interacting proteins, Crystallin Alpha B and Vimentin, mechanistically contribute to pericyte dysfunction in diabetic conditions?

The identified LBH-interacting proteins, Crystallin Alpha B and Vimentin, play crucial roles in pericyte dysfunction in diabetic conditions. Crystallin Alpha B is known to be involved in maintaining cytoskeletal integrity and cellular stress responses. In diabetic pericytes, the interaction between LBH and Crystallin Alpha B may be disrupted, leading to cytoskeletal instability and impaired stress response mechanisms. This could result in decreased pericyte function, affecting their ability to support angiogenesis and neurovascular regeneration in the corpus cavernosum. On the other hand, Vimentin is a key component of the intermediate filament network in pericytes, contributing to their structural integrity and cellular motility. In diabetic conditions, alterations in the LBH-Vimentin interaction may compromise the structural stability and migratory capacity of pericytes, further exacerbating their dysfunction and impacting erectile function.

Q: What other cell types or signaling pathways could be targeted to restore pericyte function and improve erectile function in diabetic patients?

In addition to targeting pericytes directly, several other cell types and signaling pathways could be considered to restore pericyte function and improve erectile function in diabetic patients. Endothelial cells play a crucial role in regulating blood flow and vascular homeostasis in the corpus cavernosum. Targeting endothelial cell dysfunction, which is common in diabetic ED, could enhance the microenvironment for pericyte function. Additionally, targeting smooth muscle cells, which are involved in maintaining penile rigidity during erection, could indirectly support pericyte function by improving overall tissue integrity. Signaling pathways such as the nitric oxide pathway, which is essential for vasodilation and erectile function, could also be targeted to enhance pericyte-mediated angiogenesis and neurovascular regeneration in diabetic conditions.

Q: Given the importance of pericytes in the corpus cavernosum, how might pericyte-targeted therapies be developed and integrated into the treatment of diabetic erectile dysfunction?

Developing pericyte-targeted therapies for diabetic erectile dysfunction requires a comprehensive understanding of pericyte biology and their interactions within the cavernous microenvironment. One approach could involve utilizing gene therapy or small molecule inhibitors to modulate the expression of key pericyte-specific genes, such as LBH, to restore their function in diabetic conditions. Targeting signaling pathways that regulate pericyte behavior, such as the PDGF-BB pathway, could also be a viable strategy to enhance pericyte function and promote tissue repair in the corpus cavernosum. Integrating pericyte-targeted therapies with existing treatments for diabetic ED, such as phosphodiesterase 5 inhibitors, could offer a synergistic approach to improving erectile function by addressing both vascular and cellular components of the disease. Collaborative efforts between researchers, clinicians, and pharmaceutical companies will be essential to translate these findings into effective pericyte-targeted therapies for diabetic erectile dysfunction.

Konsep Inti

Pericyte dysfunction, characterized by reduced expression of genes involved in collagen/ECM organization and angiogenesis, is a key contributor to the pathogenesis of diabetic erectile dysfunction.

Abstrak

The study used single-cell RNA sequencing to analyze the cellular landscape and transcriptional changes in cavernous tissues under diabetic conditions. Key findings:

Decreased expression of genes associated with collagen/ECM organization and angiogenesis was observed in diabetic fibroblasts, chondrocytes, myofibroblasts, valve-related lymphatic endothelial cells, and pericytes.
The pericyte-specific marker Lbh was identified, which clearly distinguishes pericytes from smooth muscle cells in mouse and human cavernous tissues.
Cell-cell interaction analysis revealed that pericytes play a crucial role in angiogenesis, adhesion, and migration by communicating with other cell types in the corpus cavernosum, but these interactions were highly reduced under diabetic conditions.
Lbh expression was low in diabetic pericytes, and overexpression of LBH prevented erectile function by regulating neurovascular regeneration.
The LBH-interacting proteins Crystallin Alpha B and Vimentin were identified in mouse cavernous pericytes, indicating that their interactions are critical for maintaining pericyte function.

The study provides novel insights into the pathogenesis of diabetic erectile dysfunction, highlighting pericyte dysfunction as a key driver and identifying potential therapeutic targets.

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biorxiv.org

Statistik

Decreased expression of genes associated with collagen/ECM organization and angiogenesis in diabetic fibroblasts, chondrocytes, myofibroblasts, valve-related lymphatic endothelial cells, and pericytes.
Lbh is a pericyte-specific marker that distinguishes pericytes from smooth muscle cells.
Reduced cell-cell interactions between pericytes and other cell types in the corpus cavernosum under diabetic conditions.
Low Lbh expression in diabetic pericytes, and overexpression of LBH prevents erectile function by regulating neurovascular regeneration.
Identification of LBH-interacting proteins Crystallin Alpha B and Vimentin in mouse cavernous pericytes.

Kutipan

"Pericytes are vital in penile erection; however, their dysfunction due to diabetes remains unclear."
"Lbh expression is low in diabetic pericytes, and overexpression of LBH prevents erectile function by regulating neurovascular regeneration."
"The LBH-interacting proteins (Crystallin Alpha B and Vimentin) were identified in mouse cavernous pericytes through LC-MS/MS analysis, indicating that their interactions were critical for maintaining pericyte function."

Wawasan Utama Disaring Dari

Single cell transcriptome analysis of cavernous tissues reveals the key roles of pericytes in diabetic erectile dysfunction

by Bae,S.-G., Y... pada www.biorxiv.org 05-26-2023

https://www.biorxiv.org/content/10.1101/2023.05.25.542355v5

Pertanyaan yang Lebih Dalam

How do the identified LBH-interacting proteins, Crystallin Alpha B and Vimentin, mechanistically contribute to pericyte dysfunction in diabetic conditions?

The identified LBH-interacting proteins, Crystallin Alpha B and Vimentin, play crucial roles in pericyte dysfunction in diabetic conditions. Crystallin Alpha B is known to be involved in maintaining cytoskeletal integrity and cellular stress responses. In diabetic pericytes, the interaction between LBH and Crystallin Alpha B may be disrupted, leading to cytoskeletal instability and impaired stress response mechanisms. This could result in decreased pericyte function, affecting their ability to support angiogenesis and neurovascular regeneration in the corpus cavernosum. On the other hand, Vimentin is a key component of the intermediate filament network in pericytes, contributing to their structural integrity and cellular motility. In diabetic conditions, alterations in the LBH-Vimentin interaction may compromise the structural stability and migratory capacity of pericytes, further exacerbating their dysfunction and impacting erectile function.

What other cell types or signaling pathways could be targeted to restore pericyte function and improve erectile function in diabetic patients?

In addition to targeting pericytes directly, several other cell types and signaling pathways could be considered to restore pericyte function and improve erectile function in diabetic patients. Endothelial cells play a crucial role in regulating blood flow and vascular homeostasis in the corpus cavernosum. Targeting endothelial cell dysfunction, which is common in diabetic ED, could enhance the microenvironment for pericyte function. Additionally, targeting smooth muscle cells, which are involved in maintaining penile rigidity during erection, could indirectly support pericyte function by improving overall tissue integrity. Signaling pathways such as the nitric oxide pathway, which is essential for vasodilation and erectile function, could also be targeted to enhance pericyte-mediated angiogenesis and neurovascular regeneration in diabetic conditions.

Given the importance of pericytes in the corpus cavernosum, how might pericyte-targeted therapies be developed and integrated into the treatment of diabetic erectile dysfunction?

Developing pericyte-targeted therapies for diabetic erectile dysfunction requires a comprehensive understanding of pericyte biology and their interactions within the cavernous microenvironment. One approach could involve utilizing gene therapy or small molecule inhibitors to modulate the expression of key pericyte-specific genes, such as LBH, to restore their function in diabetic conditions. Targeting signaling pathways that regulate pericyte behavior, such as the PDGF-BB pathway, could also be a viable strategy to enhance pericyte function and promote tissue repair in the corpus cavernosum. Integrating pericyte-targeted therapies with existing treatments for diabetic ED, such as phosphodiesterase 5 inhibitors, could offer a synergistic approach to improving erectile function by addressing both vascular and cellular components of the disease. Collaborative efforts between researchers, clinicians, and pharmaceutical companies will be essential to translate these findings into effective pericyte-targeted therapies for diabetic erectile dysfunction.