Connective tissue and its growth factor CTGF distinguish the morphometric and molecular remodeling of the bladder in a model of neurogenic bladder
Connective tissue and its growth factor CTGF distinguish the morphometric and molecular remodeling of the bladder in a model of neurogenic bladder
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DOI：
10.1152/ajprenal.00273.2012
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发表时间：
2012-11-01
影响因子：
4.2
通讯作者：
Tuohy, Vincent K.
中科院分区：
文献类型：
--
作者：
Altuntas, Cengiz Z.;Daneshgari, Firouz;Tuohy, Vincent K.
AlTuntas CZ，Daneshgari F，Izgi K，Bisher F，Ozer A，Sakalar C，Grimberg KO，Sayin I，Tuohy VK。结缔组织及其生长因子CTGF在神经源性膀胱模型中区分膀胱的形态和分子重塑。Am J Physiol Renal Physiol 303：F1363-F1369,2012。2012年9月19日首次出版；doi：10.1152/ajprenal.00273.2012。-我们之前曾报道，患有多发性硬化症(MS)模型的实验性自身免疫性脑脊髓炎(EAE)的小鼠会出现严重的膀胱功能障碍。因为多发性硬化症患者的神经原性膀胱会导致显著的膀胱重塑，我们接下来检查了EAE小鼠的膀胱的形态和分子变化。在雌性SJL/J小鼠中，用髓鞘蛋白脂蛋白的p139-151致脑肽在完全弗氏佐剂中免疫，并腹腔注射百日咳杆菌毒素，从而产生EAE。免疫后70天，对小鼠的神经功能损害程度进行评分，然后处死。脊髓切片评估脱髓鞘、炎症和T细胞浸润；定量测量膀胱组织的成分；评估组织重塑和纤维化标志物的基因表达。随着神经功能损害的加重，膀胱体质量/体重比显著增加，形态计量学分析显示膀胱腔面积增大，组织肥大。尽管所有组织成分(尿路上皮、平滑肌和结缔组织)的数量增加，但与对照组相比，EAE小鼠的结缔组织与肌肉的比率显著增加。观察到EAE小鼠I型胶原α(2)、原弹性蛋白、转化生长因子-β3和结缔组织生长因子(CTGF)的mRNA表达显著增加，而平滑肌肌球蛋白重链、神经生长因子、M受体和嘌呤能受体的mRNAs水平降低。我们的结果提示，与EAE严重程度相对应的膀胱重塑可能是由于CTGF表达增强和结缔组织生长增加所致。
Altuntas CZ, Daneshgari F, Izgi K, Bicer F, Ozer A, Sakalar C, Grimberg KO, Sayin I, Tuohy VK. Connective tissue and its growth factor CTGF distinguish the morphometric and molecular remodeling of the bladder in a model of neurogenic bladder. Am J Physiol Renal Physiol 303: F1363-F1369, 2012. First published September 19, 2012; doi:10.1152/ajprenal.00273.2012.-We previously reported that mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), develop profound urinary bladder dysfunction. Because neurogenic bladder in MS patients causes marked bladder remodeling, we next examined morphometric and molecular alterations of the bladder in EAE mice. EAE was created in female SJL/J mice by immunization with the p139-151 encephalitogenic peptide of myelin proteolipid protein in complete Freund's adjuvant, along with intraperitoneal injections of Bordetella pertussis toxin. Seventy days after immunization, mice were scored for the level of neurological impairment and then killed. Spinal cord sections were assessed for demyelination, inflammation, and T cell infiltration; the composition of the bladder tissue was measured quantitatively; and gene expression of markers of tissue remodeling and fibrosis was assessed. A significant increase in the bladder weight-to-body weight ratio was observed with increasing neurological impairment, and morphometric analysis showed marked bladder remodeling with increased luminal area and tissue hypertrophy. Despite increased amounts of all tissue components (urothelium, smooth muscle, and connective tissue), the ratio of connective tissue to muscle increased significantly in EAE mice compared with control mice. Marked increases in mRNA expression of collagen type I alpha(2), tropoelastin, transforming growth factor-beta 3, and connective tissue growth factor (CTGF) were observed in EAE mice, as were decreased levels of mRNAs for smooth muscle myosin heavy chain, nerve growth factors, and muscarinic and purinergic receptors. Our results suggest that bladder remodeling corresponding to EAE severity may be due to enhanced expression of CTGF and increased growth of connective tissue.