Sonic hedgehog信号通路与勃起功能障碍的相关研究进展

Sonic hedgehog(Shh)是维持男性勃起功能的重要调节因子,异常的Shh信号可能是导致ED的机制之一。目前关于Shh信号通路与ED的研究主要集中在双侧海绵体神经损伤的神经源性ED,糖尿病导致的内分泌性ED以及老年性ED。本文梳理了不同类型ED中Shh信号通路的改变,阐明了Shh信号通路在ED中的调控机制,以期对今后的相关研究给予启发。     

Hh信号通路相关因子Shh、Ptch1、Gli1 mRNA的表达及意义

目的探讨前列腺癌、癌旁前列腺组织以及正常前列腺增生组织中Hedgehog(Hh)信号通路相关因子Shh、Ptch1、Gli1 mRNA的表达及意义。方法选择2017年2月至2019年2月本院收治的42例前列腺癌患者作为研究对象, 设为观察组。所有患者均拟手术治疗, 术中取癌组织与癌旁组织(距离病灶≥3 cm);选择同期手术治疗的39例前列腺增生患者的手术标本, 设为对照组。利用免疫组化和qRT-PCR技术检测前列腺增生、前列腺癌和癌旁组织中Hh信号通路相关因子Shh、Ptch1和Gli1蛋白及mRNA的表达情况, 分析比较Hh信号通路在前列腺增生、前列腺癌和癌旁组织中表达的差异及其机制。结果观察组的癌旁组织与对照组的Shh、Ptch1和Gli1蛋白阳性率比较, 差异均无统计学意义(均P>0.05);观察组的癌组织中Shh、Ptch1和Gli1蛋白阳性率均高于对照组(均P<0.05)。观察组的癌旁组织与对照组的Shh、Ptch1和Gli1 mRNA表达水平比较, 差异均无统计学意义(均P>0.05);观察组的癌组织中Shh、Ptch1和Gli1 mRNA表达水平均高于观...     

音猬因子信号通路与骨质疏松症关系的研究进展

骨发育的过程受到多种信号通路的调节,如Wnt、Notch、BMP、Hedgehog信号通路等。Hedgehog信号通路对骨形成的作用在过去的二十几年已经被证实。音猬因子(Ssonic hedgehog,Shh)在Hedgehog家族中表达最广泛,在该信号传导通路上对轴骨、四肢骨、颅面骨等骨骼的形成起着重要作用。骨质疏松症发病机制归根到底是成骨细胞的骨形成能力与破骨细胞的骨吸收之间的平衡被打破,并且成骨细胞的骨形成作用下降是其主要影响因素之一。本文主要从分子水平对Shh信号通路与影响骨质疏松症发生的几个主要因素进行综述,为Shh信号通路应用于骨质疏松的防治提供理论依据。     

酪蛋白激酶2(CK2)及其在良性前列腺增生中的意义

酪蛋白激酶 2 (CK2 )是蛋白激酶家族中的特殊成员 ,主要作用是催化蛋白磷酸化调节蛋白功能 ,是至今所知的最多效性的蛋白激酶之一。CK2是细胞内重要的生长刺激传递信号 ,富含于胚胎、肿瘤及增生组织。本文简介了CK2的分子结构、功能区及其在细胞内的作用机制。前列腺中CK2可受性激素和生长因子敏感调节。良性前列腺增生 (BPH)组织中CK2活性远高于前列腺癌和正常前列腺组织 ,突出了CK2在BPH中的重要性。深入研究CK2在前列腺增生中的作用机制可以为临床治疗BPH的抗CK2方向提供理论基础。     

酪蛋白激酶2（CK2）及其在良性前列腺增生中的意义

酪蛋白激酶2（CK2）是蛋白激酶家族中的特殊成员，主要作用是催化蛋白磷化调节蛋白功能，是至今所知的最多效性的蛋白激酶之一。CK2是细胞内重要的生长刺激传递信号，富含于胚胎、肿瘤及增生组织。本文简介了CK2的分子结构、功能区及其在细胞内的作用机制。前列腺中CK2可受性激素和生长因子敏感调节。良性前列腺增生（BPH）组织中CK2活生远高于前列腺癌和正常前列腺组织，突出了CK2在BPH中的重要性。深入研究CK2在前列腺增生中的作用机制可以为临床治疗BPH的抗CK2方向提供理论基础。     

Hedgehog信号通路效应蛋白在前列腺癌组织中的表达及意义

目的 探讨Hedgehog(Hh)信号通路中效应蛋白在人前列腺癌、癌旁正常前列腺组织中的表达及意义.方法 采用免疫组织化学方法检测51例前列腺癌和癌旁正常前列腺组织中Shh、Ptch1和Gli1的表达.结果 Shh、Ptch1和Gli1在前列腺癌组织中均为高表达,Shh与Ptch1的表达呈正相关.结论 在前列腺癌Hh信号通路中Shh、Ptch1和Gli1呈现高度表达状态,Gti1更能准确地反映前列腺癌细胞的增殖水平和分化程度.     

前列腺疾病相关miRNA表达的研究进展

miRNA是一类具有约22个核苷酸的非编码RNA,可以调控各种生物学过程,并调节细胞和基因表达,在细胞和疾病发展过程中发挥巨大作用。近年来,miRNA在前列腺疾病中发挥的作用成为研究热门。通过研究miRNA表达与前列腺疾病之间的关系,可以帮助我们更好的从分子生物学角度认识前列腺疾病,阐释其发病机制,并指导临床治疗及预后。目前,对于前列腺癌相关的miRNA研究较多,涉及疾病的发生、发展、发病机制、诊断、预后和治疗等多个方面。而在前列腺炎和良性前列腺增生方面,相关miRNA表达的研究则相对较少。本文简述miRNA的起源、生物学作用,并回顾了近年来相关miRNA在前列腺炎、良性前列腺增生及前列腺癌中的表达的研究进展,旨在帮助进一步了解miRNA在前列腺疾病中所发挥的作用及相关机制,为临床诊疗前列腺疾病提出新思路,并为未来miRNA在前列腺疾病中的研究提出新见解。     

siRNA沉默Rab23基因对胰腺癌细胞PANC-1增殖和凋亡的影响

Sonic hedgehog(Shh)信号通路是在动物胚胎发育过程中调节细胞间相互作用的重要信号分子之一,在胰腺癌的发生发展过程中发挥重要作用[1].Rab23是该信号通路副调控基因[2],其功能受到抑制后会导致hedgehog信号通路活性受阻.该研究设计针对Rab23基因的siRNA将其沉默,观察对胰腺癌细胞PANC-1增殖和凋亡的影响,为胰腺癌的临床诊断、治疗及预后提供依据.     

性激素与慢性无菌性前列腺炎发生的研究进展

慢性无菌性前列腺炎是多因素引起的前列腺炎症,临床上以盆底痛、排尿刺激症状和性功能障碍为主要表现。前列腺是性激素依赖的男性内生殖器,体内性激素水平在调节前列腺的生长、功能和前列腺疾病发生中起重要作用。动物实验中,雌二醇水平增高是引起无菌性前列腺炎发生的本质,雄激素水平下降也能诱发前列腺炎,而高于生理剂量的睾酮能够减轻前列腺内炎症反应。但目前仍然缺乏性激素在人类无菌性前列腺炎发生中作用的临床证据。     

前列腺素合成酶基因调控与前列腺疾病关系的研究进展

前列腺素合成酶(PGS)能催化各种类型前列腺素的生成,调节相关物质的基因表达水平,其基因调控机制与前列腺疾病的发生和发展密切相关。目前有关PGS在前列腺疾病如良性前列腺增生(BPH)和前列腺癌(PCa)中调控机制的研究很少,鲜有研究直接对PGS基因调控与前列腺疾病关系进行探讨。本文拟对两者的关系进行分析,为从干预PGS调控途径防控BPH和PCa提供研发思路。     

Hedgehog signaling is essential for normal wound healing

The hedgehog family of morphogens (sonic [Shh], Indian, and desert hedgehog) are central regulators of embryologic growth and tissue patterning. Although recent work implicates Shh in postnatal tissue repair and development, conclusive evidence is lacking. Here, we demonstrated the importance of Shh in wound repair, by examining the effects of cyclopamine, a specific inhibitor of the Shh signaling cascade, on tissue repair. Using a murine‐splinted excisional wound model, which attenuates wound contraction in this loose‐skinned rodent, we established that, by all measures (wound closure, epithelialization, granulation formation, vascularity, and proliferation), wound healing was profoundly impaired when Shh signaling was disrupted. Because embryonic disruption of Shh is associated with distinct phenotypic defects, our findings invite investigation of the potential role of Shh signaling under postnatal conditions associated with disregulated wound healing.     

Sonic Hedgehog Is a Novel Tubule-Derived Growth Factor for Interstitial Fibroblasts after Kidney Injury

Tubular epithelium constitutes the majority of the renal parenchyma and is the primary target of various kidney injuries. However, how the injured tubules drive interstitial fibroblast activation and proliferation remains poorly understood. Here, we investigated the role of sonic hedgehog (Shh), a secreted extracellular signaling protein, in fibroblast proliferation. Shh was induced in renal tubular epithelia in animal models of CKD induced by ischemia/reperfusion injury (IRI), adriamycin, or renal mass ablation, and in renal tubules of kidney biopsy specimens from CKD patients with different etiologies. Using Gli1-CreER^T2 reporter mice, we identified interstitial fibroblasts as the principal targets of renal Shh signaling in vivo. In vitro, incubation with Shh promoted normal rat kidney fibroblast proliferation, which was assessed by cell counting, MTT assay, and BrdU incorporation assay, and stimulated the induction of numerous proliferation-related genes. However, Shh had no effect on the proliferation of renal tubular epithelial cells. In vivo, overexpression of Shh promoted fibroblast expansion and aggravated kidney fibrotic lesions after IRI. Correspondingly, blockade of Shh signaling by cyclopamine, a small molecule inhibitor of Smoothened, inhibited fibroblast proliferation, reduced myofibroblast accumulation, and attenuated renal fibrosis. These studies identify Shh as a novel, specific, and potent tubule-derived growth factor that promotes interstitial fibroblast proliferation and activation. Our data also suggest that blockade of Shh signaling is a plausible strategy for therapeutic intervention of renal fibrosis.     

Hedgehog signaling in the prostate

PURPOSE: Recent discoveries highlight the importance of the hedgehog signaling pathway in prostate growth regulation. We reviewed the role of hedgehog signaling in prostate development, adult prostate homeostasis and prostate cancer. MATERIALS AND METHODS: A comprehensive review of all relevant literature was done. RESULTS: Epithelial expression of hedgehog ligand during prostate development exerts autocrine and paracrine signaling activities that regulate growth and differentiation. Hedgehog signaling also occurs in the adult human prostate but to our knowledge the influence on epithelial proliferation and/or differentiation is unknown. Robust hedgehog signaling occurs frequently in prostate cancer, and autocrine and paracrine signaling have been shown to accelerate the growth of xenograft tumors. Autocrine signaling has been implicated in stimulating stem/progenitor cells and increased hedgehog pathway activity may be a characteristic of advanced, androgen independent cancer. The plant alkaloid cyclopamine is a specific chemical inhibitor of hedgehog signaling that produced sustained regression of established xenograft tumors. CONCLUSIONS: Hedgehog signaling has an important role in prostate development and it appears to be a characteristic feature of prostate cancer. It stimulates tumor growth and may exert a specific role in the proliferation of tumor stem cells. The development of hedgehog inhibitors based on the action of cyclopamine holds promise for novel treatments to slow or arrest tumor growth.     

Sonic hedgehog protein promotes proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro

Background Sonic hedgehog (Shh) protein is known to be an important signaling protein in early embryonic development. Also, Shh is involved in the induction of early cartilaginous differentiation of mesenchymal cells in the limb and in the spine. Methods The impact of Shh on adult stem cells, human bone marrow-derived mesenchymal stem cells (MSCs), was tested. The MSCs were treated either with recombinant Sonic hedgehog protein (r-Shh) or with transforming growth factor-beta 1 (TGF-β₁) as a positive control in vitro for 3 weeks. The effects on cartilaginous differentiation and proliferation were assayed. Results MSCs when treated with either Shh or TGF-β₁ showed expression of cartilage markers aggrecan, Sox9, CEP-68, and collagen type II and X within 3 weeks. Only r-Shh-treated cells showed a very strong cell proliferation and much higher BrdU incorporation in cell assay systems. Conclusions These are the first data that indicate an important role of Shh for the induction of cartilage production by MSCs in vitro.     

Hedgehog signaling in prostate growth and benign prostate hyperplasia

Hedgehog (Hh) signaling has long been recognized for its role in axial patterning, mesenchymal-epithelial inductive signaling, and growth regulation during fetal development. In many embryonic tissues, Hh functions as a proliferative stimulus. Sonic hedgehog and Indian hedgehog are both expressed by the urothelium of the fetal prostate anlage, where they regulate cell proliferation and differentiation and play a role in prostate ductal budding. Whereas Hh signaling in mouse prostate diminishes during adolescence and is maintained at a low level in the adult, robust Hh signaling is commonly found in the adult human prostate. The reason(s) for robust Hh signaling in the adult human prostate and the actions of Hh signaling on growth and differentiation in the adult are not well understood. However, increased Hh signaling has been associated with prostate cancer and has been shown to accelerate prostate cancer growth. These observations suggest that inappropriate reawakening of this developmental growth signal may play a pivotal role in prostate neoplasia. This review examines the role of Hh signaling during early prostate growth and in its corollary actions during prostate disease, including benign prostate hyperplasia and prostate cancer. The use of Hh inhibitors as a therapeutic modality for androgen-independent treatment of prostate disease is also discussed.     

特异性阻断Shh信号通路对肝细胞癌细胞系Hep-3B增殖和凋亡的影响

目的 观察阻抑胚胎发育相关信号通路Sonic hedgehog(Shh)对人肝癌细胞系Hep-3B增殖和凋亡的影响.方法 将实验细胞分为转染组、隐性对照组和空白对照组.设计针对Shh信号通路中Smo基因的siRNA,通过Lipedectemin2000将其转染进Hep-3B细胞株,噻唑蓝(Mar)比色法检测沉默Smo基因后第0、8、16、24和48 h的细胞数和MTr的D(入)值;流式细胞术检测沉默Smo基因48 h细胞凋亡.结果 转染组与空白对照组比较,加入siRNA后,8 h时细胞增殖数无明显减少,16、24和48 h时细胞数明显减少(P<0.01),24和48 h时细胞存活率差异有统计学意义.阴性对照组与空白对照组比较,差异无统计学意义(P>0.05);Hep-3B细胞经siRNA作用48 h后,可见亚二倍体核型峰-凋亡峰.其中,转染组凋亡率为30%,阴性对照组与空白对照组未见凋亡峰.结论 Shh信号分子对肝细胞癌的增殖起维持作用;通过特异性阻断该信号通路,可以抑制肝癌细胞增殖,并促进细胞凋亡.