PDF(Pubmed)
Abstract：
As a peripheral nerve injury disease, cavernous nerve injury (CNI) caused by prostate cancer surgery and other pelvic surgery causes organic damage to cavernous blood vessels and nerves, thereby significantly attenuating the response to phosphodiesterase-5 inhibitors. Here, we investigated the role of heme-binding protein 1 (Hebp1) in erectile function using a mouse model of bilateral CNI, which is known to promote angiogenesis and improve erection in diabetic mice. We found a potent neurovascular regenerative effect of Hebp1 in CNI mice, demonstrating that exogenously delivered Hebp1 improved erectile function by promoting the survival of cavernous endothelial-mural cells and neurons. We further found that endogenous Hebp1 delivered by mouse cavernous pericyte (MCP)-derived extracellular vesicles promoted neurovascular regeneration in CNI mice. Moreover, Hebp1 achieved these effects by reducing vascular permeability through regulation of claudin family proteins. Our findings provide new insights into Hebp1 as a neurovascular regeneration factor and demonstrate its potential therapeutic application to various peripheral nerve injuries.
摘要：
作为一种周围神经损伤疾病,由前列腺癌手术和其他盆腔手术引起的海绵状神经损伤（CNI）会对海绵状血管和神经造成器质性损害，从而显著减弱对磷酸二酯酶-5抑制剂的反应。这里,我们使用双侧CNI小鼠模型研究血红素结合蛋白1（Hebp1）在勃起功能中的作用，已知它能促进血管生成和改善糖尿病小鼠的勃起。我们发现Hebp1在CNI小鼠中具有强大的神经血管再生作用，证明外源递送的Hebp1通过促进海绵状内皮壁细胞和神经元的存活来改善勃起功能。我们进一步发现，由小鼠海绵状周细胞（MCP）衍生的细胞外囊泡递送的内源性Hebp1促进CNI小鼠的神经血管再生。此外，Hebp1通过调节claudin家族蛋白降低血管通透性来实现这些作用。我们的发现为Hebp1作为神经血管再生因子提供了新的见解，并证明了其在各种周围神经损伤中的潜在治疗应用。
