Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity.
Molecular and functional characterization of detrusor PDGFRα positive cells in spinal cord injury-induced detrusor overactivity.
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DOI：
10.1038/s41598-021-95781-2
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发表时间：
2021-08-11
影响因子：
4.6
通讯作者：
Koh SD
中科院分区：
文献类型：
--
作者：
Lee K;Park SO;Choi PC;Ryoo SB;Lee H;Peri LE;Zhou T;Corrigan RD;Yanez AC;Moon SB;Perrino BA;Sanders KM;Koh SD
容量调节是通过一种涉及逼尿肌间质细胞的新机制发生的。膀胱中的间质细胞为PDGFRα+，它们将平滑肌的兴奋性抑制在低水平，并防止短暂性收缩（TC）的发生。脊髓损伤（SCI）引起的膀胱功能障碍的常见临床表现是逼尿肌过度活动（DO）。尽管已经提出 SCI 后 DO 的肌源性起源，但 SCI 诱导 DO 的发展机制尚未确定。在这项研究中，我们假设 SCI 诱导的 DO 与 PDGFRα+ 细胞提供的调节机制功能丧失有关。我们的结果表明 SCI 后 Pdgfra 和 Kcnn3 的转录表达下降。 SCI 后这些基因编码的蛋白质也减少，PDGFRα+ 细胞密度也减少。 PDGFRα+细胞的损失是由于细胞凋亡造成的。 SCI 后充盈期间离体膀胱中的 TC 急剧增加，这与 SK 通道提供的调节丧失有关，因为我们观察到对 apamin 的敏感性降低。这些发现表明，PDGFRα+ 细胞在膀胱充盈过程中抑制肌肉收缩的机制受到损害，是 SCI 后 DO 发生的原因。
Volume accommodation occurs via a novel mechanism involving interstitial cells in detrusor muscles. The interstitial cells in the bladder are PDGFRα+, and they restrain the excitability of smooth muscle at low levels and prevents the development of transient contractions (TCs). A common clinical manifestation of spinal cord injury (SCI)-induced bladder dysfunction is detrusor overactivity (DO). Although a myogenic origin of DO after SCI has been suggested, a mechanism for development of SCI-induced DO has not been determined. In this study we hypothesized that SCI-induced DO is related to loss of function in the regulatory mechanism provided by PDGFRα+ cells. Our results showed that transcriptional expression of Pdgfra and Kcnn3 was decreased after SCI. Proteins encoded by these genes also decreased after SCI, and a reduction in PDGFRα+ cell density was also documented. Loss of PDGFRα+ cells was due to apoptosis. TCs in ex vivo bladders during filling increased dramatically after SCI, and this was related to the loss of regulation provided by SK channels, as we observed decreased sensitivity to apamin. These findings show that damage to the mechanism restraining muscle contraction during bladder filling that is provided by PDGFRα+ cells is causative in the development of DO after SCI.
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影响因子：
4.3
作者：
Li W;Sasse KC;Bayguinov Y;Ward SM;Perrino BA
通讯作者：
Perrino BA
影响因子：
5.3
作者：
Koh BH;Roy R;Hollywood MA;Thornbury KD;McHale NG;Sergeant GP;Hatton WJ;Ward SM;Sanders KM;Koh SD
通讯作者：
Koh SD
影响因子：
5.3
作者：
Gevaert T;Ridder D;Vanstreels E;Daelemans D;Everaerts W;Aa FV;Pintelon I;Timmermans JP;Roskams T;Steiner C;Neuhaus J
通讯作者：
Neuhaus J
影响因子：
4.6
作者：
Lee, Haeyeong;Koh, Byoung H.;Koh, Sang Don
通讯作者：
Koh, Sang Don
影响因子：
7.3
作者：
McCloskey, K. D.;Anderson, U. A.;Ward, S. M.
通讯作者：
Ward, S. M.