Peptide amphiphile nanofiber hydrogel delivery of Sonic hedgehog protein to the penis and cavernous nerve suppresses intrinsic and extrinsic apoptotic signaling mechanisms, which are an underlying cause of erectile dysfunction.
Peptide amphiphile nanofiber hydrogel delivery of Sonic hedgehog protein to the penis and cavernous nerve suppresses intrinsic and extrinsic apoptotic signaling mechanisms, which are an underlying cause of erectile dysfunction.
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DOI：
10.1016/j.nano.2021.102444
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Podlasek CA
中科院分区：
文献类型：
--
作者：
Martin S;Harrington DA;Ohlander S;Stupp SI;McVary KT;Podlasek CA
勃起功能障碍 (ED) 是一种常见且令人衰弱的疾病，对生活质量影响很大。 ED 的一个根本原因是阴茎平滑肌细胞凋亡，这种情况在前列腺切除术、糖尿病和老年患者中随海绵体神经损伤而发生。我们正在开发肽两亲物 (PA) 纳米纤维水凝胶，作为 Sonic Hedgehog 蛋白体内递送载体到阴茎和海绵体神经，以防止细胞凋亡反应。我们研究了生物材料临床应用所需的两个重要方面，SHH PA 是否抑制内在（半胱天冬酶 9）和外在（半胱天冬酶 8）凋亡机制，以及抑制一种凋亡机制是否通过不同机制迫使细胞凋亡发生。我们表明，SHH PA 抑制 caspase 9 和 8 凋亡机制，并且抑制 caspase 9 不会将信号转移到 caspase 8。SHH PA 通过管理内在和外在凋亡机制，作为预防性 ED 治疗具有显着的临床潜力。勃起功能障碍 (ED) 是一种常见且令人衰弱的疾病，对生活质量影响很大。 ED 的一个根本原因是阴茎平滑肌细胞凋亡，这种情况在前列腺切除术、糖尿病和老年患者中随海绵体神经损伤而发生。我们正在开发肽两亲物 (PA) 纳米纤维水凝胶，作为 Sonic Hedgehog 蛋白到阴茎和海绵体神经的体内递送载体，以防止细胞凋亡反应和 ED。我们研究了生物材料临床应用所需的两个重要方面，SHH PA 是否抑制内在（半胱天冬酶 9）和外在（半胱天冬酶 8）凋亡机制，以及抑制一种凋亡机制是否通过不同机制迫使细胞凋亡发生。我们表明，SHH PA 抑制 caspase 9 和 8 凋亡机制，并且抑制 caspase 9 不会将信号转移到 caspase 8。SHH PA 通过管理内在和外在凋亡机制，作为预防性 ED 治疗具有显着的临床潜力。
Erectile dysfunction (ED) is a common and debilitating condition with high impact on quality of life. An underlying cause of ED is apoptosis of penile smooth muscle, which occurs with cavernous nerve injury, in prostatectomy, diabetic and aging patients. We are developing peptide amphiphile (PA) nanofiber hydrogels as an in vivo delivery vehicle for Sonic hedgehog protein to the penis and cavernous nerve to prevent the apoptotic response. We examine two important aspects required for clinical application of the biomaterials, if SHH PA suppresses intrinsic (caspase 9) and extrinsic (caspase 8) apoptotic mechanisms, and if suppressing one apoptotic mechanism forces apoptosis to occur via a different mechanism. We show that SHH PA suppresses both caspase 9 and 8 apoptotic mechanisms, and suppressing caspase 9 did not shift signaling to caspase 8. SHH PA has significant clinical potential as a preventative ED therapy, by management of intrinsic and extrinsic apoptotic mechanisms. Erectile dysfunction (ED) is a common and debilitating condition with high impact on quality of life. An underlying cause of ED is apoptosis of penile smooth muscle, which occurs with cavernous nerve injury, in prostatectomy, diabetic and aging patients. We are developing peptide amphiphile (PA) nanofiber hydrogels as an in vivo delivery vehicle for Sonic hedgehog protein to the penis and cavernous nerve to prevent the apoptotic response and ED. We examine two important aspects required for clinical application of the biomaterials, if SHH PA suppresses intrinsic (caspase 9) and extrinsic (caspase 8) apoptotic mechanisms, and if suppressing one apoptotic mechanism forces apoptosis to occur via a different mechanism. We show that SHH PA suppresses both caspase 9 and 8 apoptotic mechanisms, and suppressing caspase 9 did not shift signaling to caspase 8. SHH PA has significant clinical potential as a preventative ED therapy, by management of intrinsic and extrinsic apoptotic mechanisms.
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影响因子：
6.6
作者：
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作者：
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ED患者和动物模型中的caspase信号传导。
DOI：
10.1016/j.jsxm.2021.01.175
发表时间：
2021-04
期刊：
The journal of sexual medicine
影响因子：
--
作者：
Martin S;Harrington DA;Ohlander S;Stupp SI;McVary KT;Podlasek CA
通讯作者：
Podlasek CA