Research progress on the development of hepatocyte growth factor/c-Met signaling pathway in gastric cancer:A review

Hepatocyte growth factor(HGF)and its receptor,c-Met,play important roles in the occurrence,development,and treatment of gastric cancer(GC).This review explored the function of the HGF/c-Met signaling pathway in GC and its potential targeted therapeutic mechanisms.As one of the most common malignant tumors worldwide,GC has a complex pathogenesis and limited therapeutic options.Therefore,a thorough understanding of the molecular mechanism of GC is very important for the development of new therapeutic methods.The HGF/c-Met signaling pathway plays an important role in the proliferation,migration,and invasion of GC cells and has become a new therapeutic target.This review summarizes the current research progress on the role of HGF/c-Met in GC and discusses targeted therapeutic strategies targeting this signaling pathway,providing new ideas and directions for the treatment of GC.

Gene expression of hepatocyte growth factor and its receptor in HCC and nontumorous liver tissues

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Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma and its therapeutic implications

Hepatocellular carcinoma(HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor(HGF)/c-mesenchymal-epithelial transition receptor(c-Met) axis is a key signaling pathway in HCC, either via canonical or non-canonical pathways. Available treatments against HCC based upon HGF/c-Met inhibition can increase patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c-Met monomers can bind other receptor monomers, activating several noncanonical signaling pathways, leading to increased cell proliferation, invasion, motility, and drug resistance. All of these processes are enhanced by the tumor microenvironment, with stromal cells contributing to boost tumor progression through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and fibrosis. Novel treatments against HCC are being explored to modulate other targets such as microR NAs, methyltransferases, and acetyltransferases, which are all involved in the regulation of gene expression in cancer. This review compiles basic knowledge regarding signaling pathways in HCC, and compounds already used or showing potential to be used in clinical trials.

Association of hepatocyte-derived growth factor receptor/caudal type homeobox 2 co-expression with mucosal regeneration in active ulcerative colitis

AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODS:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were collected.After preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were performed.Immunostained samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module software.For semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± SD were determined.In case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± SD) was determined.Using 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were collected.Gene expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).RESULTS:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P < 0.05),CDX2(blood:0 vs 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P < 0.05),CD133(blood:1.1 ± 0.72 vs 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P < 0.05)and Musashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to controls.HGFR/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P < 0.05)and Musashi-1/CDX2(blood and LP:0 vs scattered) coexpressions were found in blood and lamina propria of UC samples.HGFR/CD133 and CD133/CDX2 coexpressions appeared only in UC lamina propria samples.CDX2,Lgr5 and Musashi-1 expressions in UC blood samples were not accompanied by CK20 mRNA expression.CONCLUSION:In active UC,a portion of circulating HGFR-expressing cells are committed to the epithelial lineage,and may participate in mucosal regeneration by undergoing mesenchymal-to-epithelial transition.

Hepatocyte growth factor gene therapy prevents radiation-induced liver damage

AIM: To transfer human HGF gene into the liver of rats by direct electroporation as a means to prevent radiationinduced liver damage.METHODS: Rat whole liver irradiation model was accomplished by intra-operative approach. HGF plasmid was injected into liver and transferred by electroporation using a pulse generator. Control rats (n = 8) received electrogene therapy (EGT) vehicle plasmid and another 8rats received HGF-EGT 100 μg 48 h before WLIR.Expression of HGF in liver was examined by RT-PCR and ELISA methods. Apoptosis was determined by TUNEL assay. Histopathology was evaluated 10 wk after whole liver irradiation.RESULTS: Marked decrease of apoptotic cells and downregulation of transforming growth factor-beta 1 (TGF-β1)mRNA were observed in the HGF-EGT group 2 d after liver irradiation compared to control animals. Less evidence of radiation-induced liver damage was observed morphologically in liver specimen 10 wk after liver irradiation and longer median survival time was observed from HGF-EGT group (14 wk) compared to control rats (5 wk). (P = 0.031).CONCLUSION: For the first time it has been demonstrated that HGF-EGT would prevent liver from radiation-induced liver damage by preventing apoptosis and down-regulation of TGF-β1.

Effects of ethanol on insulin-like growth factor-Ⅰ system in primary cultured rat hepatocytes: Implications of JNK1/2 and alcoholdehydrogenase

AIM: To evaluate the effects of ethanol on the insulin- like growth factor-Ⅰ (IGF-Ⅰ) system involved in c-Jun N-terminal kinase (JNK1/2) and alcoholdehydrogenase (ADH) activity in primary cultured rat hepatocytes. METHODS: Hepatocytes isolated from male Sprague-Dawley rats were incubated with various concentrations of ethanol for different durations of time. The cells were pretreated with SP600125 (10 μmol/L) and 4-MP (200 μmol/L), and then treated with ethanol (200 mmol/L). We then measured IGF-Ⅰ secretion, IGF-Ⅰ mRNA expression, cell viability and JNK1/2 activity by radioimmunoassay, RT-PCR, MTT assay and Western blot, respectively (n = 6). RESULTS: Ethanol induced the activity of phospho (p)-JNK1/2, reaching a maximum at 60 min and then decreasing at 180 min. The effects of ethanol on the IGF-Ⅰ system were increased at 60 min (secretion: 7.11 ± 0.59 ng/mg protein vs 4.91 ± 0.51 ng/mg, mRNA expression: 150.2% ± 10.2% vs 101.5% ± 11.3%, P = 0.045) and then decreased at 180 min (secretion: 3.89 ± 0.25 ng/mg vs 5.4 ± 0.54 ng/mg protein; mRNA expression: 41.5% ± 10.4% vs 84.7% ± 12.1%, P = 0.04), however cell viability was decreased in a dose- and time-dependent manner. SP600125 blocked the ethanol-induced changes (at 60 min). Additionally, 4-methylpyrazole prevented the ethanol-induced decreases in the IGF-Ⅰ system, cell viability and p-JNK1/2 activity (at 180 min). CONCLUSION: This study suggests that ethanol- induced p-JNK1/2 activation is associated with the IGF-Ⅰ system and cell viability in hepatocytes. Furthermore, alcohol dehydrogenase is involved in the relationship between ethanol-induced inactivation of p-JNK1/2 and the changes of the IGF-Ⅰ system and cell viability.

The significance of proto-oncogene HGF/SF receptor c-Met mRNA expression in nasopharyngeal carcinoma

Objective: To explore the expression of c-Met mRNA in nasopharyngeal carcinomas (NPC) and its relation with clinical biological behavior. Methods: In situ hybridisation was used to detect mRNA expression of c-Met in 15 cases of non-tumor nasopharyngeal (NP), 55 cases of NPC. Results: The positive rates of c-Met mRNA in NP and NPC cells were 13.3% (2/15) and 61.8% (34/55) respectively. The expression of c-Met mRNA was significantly correlated with lymph node metastasis, local invasion (skull base erosion), and clinical stage. In cases with cervical lymph node metastasis, local invasion, and clinical stage III and IV (UICC), the positive rates of expression of c-Met mRNA were significantly higher than that in those without the conditions mentioned above (P < 0.05 or P < 0.01). But it was not significantly correlated with age, gender, histo- logic grade, and cranial nerve palsy (P > 0.05). Conclusion: The abnormal expression of c-Met gene was well correlated with the biological behavior of metastasis and invasion. To detection the expression of c-Met mRNA could serve as an important index to estimate the prognosis of NPC. C-Met may be a new diagnostic/therapeutic target of NPC.

Increased hepatic expression of insulin-like growth factor-Ⅰreceptor in chronic hepatitis C

瞄准：尽管增加像胰岛素的生长因素 -- 我受体(IGF 红外) 基因表示在肝细胞癌被报导了，在长期的丙肝(CHC ) 估计 IGF 红外的研究和肝硬化是少见的。我们因此试图与 CHC 从病人在肝评估 IGF 红外和 IGF-I mRNA 表示。方法：IGF 红外和 IGF-I mRNA 内容被半量的 RT-PCR 决定， IGF 红外蛋白质表示由在以前与 CHC 从病人获得的肝的织物(34 个病人) 并且在以后的 immunohisto 化学是坚定的(10 个病人) 有 interferon-alpha 和 ribavirin 的治疗。结果：IGF 红外 mRNA 内容的增加在从所有 CHC 病人以及从与正常的肝相比跟随 orthopic 移植(评估正常的肝的一次尝试) 的 6 个尸体肝施主获得的肝的织物被观察，当没有相关修正在 IGF-I mRNA 内容被检测时。组织化学的结果显示出的免疫在 IGF 红外 mRNA 的加薪满足，这与 ductular 反应并且到在 hepatocytes 的增加的 IGF 红外表示相关。在 IGF 红外 mRNA 内容的减少在在治疗以后完成了持续 virological 反应的病人被观察，建议处于肝的损坏的改进。结论：在有 CHC 的病人的 hepatocytes 的 IGF 红外表示的起来规定能组成一次尝试刺激 hepatocyte 新生。考虑到那个肝是有 IGF-I 的高水平的机关，我们在尖锐、长期的肝的损坏以后发现增加的 IGF 红外表示加亮需要让另外的研究阐明在肝的 IGF-I 的角色新生。

c-Met抑制剂SU11274在HGF诱导不同EGFR基因型非小细胞肺癌细胞对厄罗替尼耐药的逆转作用

目的:肝细胞生长因子(hepatocyte growth factor,HGF)诱导敏感非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞对表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth facter receptor tyrosine kinase inhibitor,EGFR-TKI)厄洛替尼耐药,本研究旨在探讨c-Met抑制剂SU11274逆转HGF诱导不同EGFR基因型非小细胞肺癌细胞株对厄洛替尼耐药及逆转耐药机制。方法:选择人NSCLC细胞株PC9(EGFR突变型,敏感株)、H292(EGFR野生型,敏感株)和A549(EGFR野生型,原发性耐药株),应用厄洛替尼和SU11274(1μmol/L)单独或联合作用于HGF(40 ng/ml)诱导的细胞株,实验分为6组:C组(不加药对照组)、H组(HGF处理)、E组(厄洛替尼处理组)、S组(SU11274处理组)、HE组(HGF+厄洛替尼处理组)、HES组(HGF+厄洛替尼+SU11274处理组)。MTT法、流式细胞术分别检测不同药物处理对各细胞增殖、凋亡的影响;应用Western blotting检测不同药物处理对各细胞中c-Met及其下游通道Stat3、Akt、Erk1/2蛋白表达水平。结果:厄洛替尼对3种细胞的增殖抑制作用均呈浓度依赖性,HGF处理能够缓解厄洛替尼的增殖抑制作用(P<0.05);不同浓度厄洛替尼联合SU11274作用于HGF诱导细胞时3种细胞株存活率比厄洛替尼单独作用于HGF诱导细胞时明显降低(P<0.05);HGS组的细胞凋亡比HG组明显增加(P<0.05);HGS组的c-Met、Stat3、Akt、Erk1/2活化蛋白量比HG组明显减少。结论:c-Met抑制剂SU11274和厄洛替尼联合应用可逆转HGF诱导不同EGFR基因型非小细胞肺癌细胞对厄洛替尼耐药,其机制可能与抑制HGF活化的c-Met及其下游通道蛋白表达有关。

HGF/C-Met在舌部鳞状细胞癌的表达及其临床意义

目的:探讨肝细胞生长因子及其受体C-Met蛋白在舌鳞癌中的表达与其临床病理特征之间的关系。方法:通过免疫组化法检测10例正常舌组织、14例舌癌前病变及63例舌鳞癌中肝细胞生长因子、C-Met的表达,数据通过SPSS13.0统计软件非参数秩和检验统计。结果:肝细胞生长因子和C-Met在舌癌、舌癌前病变及正常舌组织的阳性表达率分别为84.1%、57.1%、40.0%和76.2%、35.7%、20.0%,其表达差异均具有统计学意义(P<0.05)。在中、低分化组(90.3%)及有淋巴结转移组(100%)舌鳞癌中肝细胞生长因子的阳性表达率显著高于高分化组(78.1%)及无转移淋巴结组(76.7%);在Ⅲ、Ⅳ期(82.1%)及有淋巴结转移组(85.0%)的舌鳞癌中C-Met阳性表达率显著高于Ⅰ、Ⅱ期(71.4%)及无转移淋巴结组(72.1%),表达差异均具有统计学意义(p<0.05);63例舌癌组织切片中46例HGF及C-Met都有阳性表达,其在舌鳞状细胞癌中的表达显著正相关(P<0.01)。结论:过度表达的HGF/C-Met可作为判断舌鳞状细胞癌生物学行为、恶性潜能和预测淋巴结转移趋势的参考指标。

达康灌肠方对溃疡性结肠炎大鼠肠黏膜HGF、c-Met、EGFR及PCNA表达的影响

目的研究中药达康灌肠方(简称达康方)对溃疡性结肠炎大鼠肝细胞生长因子(HGF)、肝细胞生长因子受体(c-Met)、表皮生长因子受体(EGFR)及增殖细胞核抗原(PCNA)表达的影响。方法将SD大鼠分为5组,除空白对照组外,其余大鼠采用TNBS(2,4,6-三硝基苯磺酸)法诱导大鼠溃疡性结肠炎模型。将造模成功的大鼠再分为模型组、达康方高、低剂量组和阳性药(柳氮磺吡啶片,SASP)组,各组进行相应干预。采用免疫组化定量分析(灰度值)的方法检测实验大鼠结肠组织HGF、c-Met、EGFR及PCNA的表达。结果与空白对照组比较,模型组大鼠结肠组织HGF、c-Met、EGFR及PCNA的表达差异均有统计学意义(P<0.05)。与模型组比较,达康方高剂量组及阳性药组HGF、c-Met、EGFR及PCNA的表达增强,达康方低剂量组c-Met、EGFR表达增强,差异均有统计学意义(P<0.05)。达康方高、低剂量组之间比较,HGF及EGFR表达差异有统计学意义(P<0.05)。结论中药达康灌肠方可通过干预HGF、c-Met、EGFR表达而加快结肠黏膜的修复,恢复结肠上皮屏障功能,减少黏膜上皮接触肠腔内造成炎症持续的各种抗原,减轻炎症反应,促进结肠黏膜上皮细胞增殖而修复结肠黏膜损伤。

HGF/c-met在口腔黏膜下纤维化组织中表达的研究

收集早、中、晚期口腔黏膜下纤维性变(oral submucous fibrosis,OSF)组织各10例及正常的口腔颊黏膜组织5例,采用免疫组化SABC法对各种组织中的HGF及c-met的表达情况进行检测。结果显示在正常的口腔颊黏膜组织中HGF和c-met呈阳性表达,早、中、晚期OSF组织中表达明显降低(P<0.05)。说明HGF/c-met在OSF组织中表达受到抑制,促进了OSF的发病。

C-Met蛋白与HGF蛋白在舌鳞癌细胞中的表达及临床意义

目的探讨C-Met蛋白与肝细胞生长因子(HGF)蛋白在舌鳞癌细胞中的表达及临床意义。方法选取2011年6月至2013年5月我院口腔科收治的舌鳞癌患者46例作为实验组,另取同期在我院进行良性肿瘤切除患者27例作为对照组,正常组织为正常组,均进行免疫组化测定C-Met蛋白及HGF蛋白的表达。结果实验组中C-Met的阴性表达率为21.7%(10/46),弱阳性表达率为26.1%(12/46),强阳性表达率52.2%(24/46);对照组的阴性表达率为77.8%(21/27),弱阳性表达率为15.8%(5/27),强阳性表达率为3.7%(1/27),两组比较差异具有统计学意义(P<0.001)。实验组中HGF蛋白的阴性表达率为17.4%(8/46),弱阳性表达率为58.7%(27/46),强阳性表达率23.9%(11/46);对照组阴性表达率为63.0%(17/27),弱阳性表达率为37.0%(10/27),强阳性表达率为0.0%(0/27),两组比较差异具有统计学意义(P<0.001)。C-Met蛋白的表达与淋巴结转移比较,差异具有统计学意义(P<0.05);HGF蛋白的表达与病理分级、淋巴结转移等比较,差异具有统计学意义(P<0.05)。结论 C-Met蛋白及HGF蛋白在舌鳞癌细胞中有显著性表达,且与舌鳞癌的发生、发展有密切关系。

溃疡性结肠炎结肠黏膜修复中HGF,c-Met,EGFR的作用

目的:观察并分析肝细胞生长因子(HGF)及其受体c-Met与表皮生长因子受体(EGFR)在溃疡性结肠炎(UC)活动和非活动阶段患者结肠黏膜的表达情况,探讨其表达的临床意义．方法:根据改良Williams疾病活动指数(DAI) 将42例UC患者分为活动期(n=25)和非活动期(n=17)2组,对照组(n=20)为门诊健康体检者或肠易激综合征患者．结肠镜下活检各组患者结肠黏膜组织,采用免疫组化SABC法检测各组患者结肠黏膜HGF及c-Met表达;SP法检测EGFR及增殖细胞核抗原(PCNA)表达．结果:对照组、活动期UC患者、非活动期 UC患者HGF阳性表达率分别为22％,88％, 100％(X2=62．84,P<0．01);c-Met阳性表达率分别为25％,92％,100％(X2=62．34,P<0．01); EGFR阳性表达率分别为25％,92％,1 00％(X2 =54．34,P<0．01);PCNA过表达率分别为0, 36％,100％(X2=67．50,P<0．01),组间比较差异显著．HGF,c-Met和EGFR在UC患者结肠黏膜表达与PCNA过表达正相关(r=0．648,0．645, 0．565,P<0．01)．结论:HGF,c-Met,EGFR及PCNA在非活动期UC患者结肠黏膜中的表达较活动期UC患者和对照组明显增加．HGF及其受体c-Met与 EGFR在UC患者结肠炎症黏膜修复过程中可能起一定作用．

实时荧光定量PCR检测宫颈癌组织中HGF mRNA和c-Met mRNA的表达

目的检测宫颈癌组织中肝细胞生长因子(HGF)及其受体原癌基因c-Met的分子表达水平,并探讨其临床意义。方法采用实时荧光定量PCR(QRT-PCR)技术检测43例宫颈癌,30例宫颈上皮内瘤变Ⅲ和27例正常宫颈组织标本中HGF和c-Met的分子表达水平。结果 HGF mRNA和c-Met mRNA在宫颈癌组织中均呈高表达,其与宫颈癌患者临床分期、肿瘤直径大小、浸润深度、淋巴结转移有关(P均<0.05),而与肿瘤的分化程度无关(P>0.05)。HGF mRNA和c-Met mRNA之间存在正相关(r=0.666,P<0.01)。结论 QRT-PCR技术可对宫颈癌组织中的HGF mRNA和c-Met mRNA表达进行定量检测;HGF mRNA和c-Met mRNA的高表达与宫颈癌的侵袭转移有关。两者联合监测有利于早期诊断宫颈癌,为宫颈癌的治疗和预后提供参考。

培养的人眼小梁细胞HGF和c-met的表达

目的 观察体外培养的人眼小梁细胞肝细胞生长因子 (HGF)和其受体 (c- m et)的表达。方法 成人眼小梁细胞原代培养 ,RT- PCR检测 HGF和 c- met m RNA的表达 ,免疫组织化学染色法检测 HGF和 c- met蛋白的表达 ,酶联免疫吸附法 (Elisa)检测小梁细胞分泌 HGF蛋白。结果 RT- PCR产物为 2 6 2 bp和 30 4 bp的条带 ,为 HGF和 c- met m RNA表达阳性 ;免疫组织化学染色细胞浆呈棕色 ,为 HGF蛋白阳性表达 ,细胞膜呈棕色 ,为 c- m et蛋白阳性表达 ;Elisa法在培养的小梁细胞上清液中检测出 HGF。结论 培养的人眼小梁细胞表达 HGF和 c- m et m

HGF、C-Met在子宫内膜异位症患者在位子宫内膜的表达及意义

目的:探讨肝细胞生长因子(H G F)及其受体(C-M et)与子宫内膜异位症发病机制的关系。方法:采用链霉素抗生物素蛋白-过氧化物酶(S-P)法检测45例(增生期20例,分泌期25例)盆腔子宫内膜异位症及30例(增生期12例,分泌期18例非子宫内膜异位症妇女的在位子宫内膜的H G F与C-M et的免疫表达水平。结果:(1)盆腔子)宫内膜异位症的在位子宫内膜的H G F、C-M et表达水平显著增高P=0.006,P=0.001)。(2)H G F与C-M et呈正相(关(异位症及对照组r均为0.945)。(3)H G F与C-M et均随月经发生周期性变化(分泌期高于增生期,对照组H G F、C-M et分别为P=0.015、P=0.023;内异症组H G F、C-M et分别为P=0.003、P=0.015)。结论:类似肿瘤转移和浸润机制,H G F/C-M et系统可能参与了子宫内膜异位症的发病。

HGF/c-Met及MVD在膀胱移行细胞癌中的表达及其临床意义

目的 :探讨膀胱移行细胞癌 (BTCC)中肝细胞生长因子 (HGF)及其受体 (c Met)、FⅧ因子 (MVD)表达的临床意义。方法 :采用免疫组化SABC法对 4 9例BTCC及 10例正常膀胱黏膜组织中HGF、c Met及MVD的表达进行观察。结果 :①随肿瘤的分期、分级的增加 ,c Met、MVD表达显著增加 (均P <0 .0 1) ;②HGF在BTCC不同分期、分级之间表达差异无显著性意义 (均P >0 .0 5 ) ;③HGF、c Met高表达同MVD表达增强显著相关 (均P <0 .0 5 ) ;④c Met、MVD高表达是患者预后不良的危险因素 (均P <0 .0 5 )。结论 :HGF/c Met在BTCC侵袭进展过程中起重要作用 。

人视网膜色素上皮细胞原代培养及HGF/c-Met的表达

目的 :探讨肝细胞生长因子 (hepatocytegrowthfactor,HGF)及其受体c Met在原代培养的人视网膜色素上皮 (retinalpigmentepithelium ,RPE)细胞中的表达情况。 方法 :体外培养人RPE细胞 ,3 5代细胞用于实验 ;采用免疫细胞化学和RT PCR方法检测细胞内HGF及其受体c Met的表达。结果 :人RPE细胞HGF及其受体c Met免疫细胞化学染色的阳性信号分别位于细胞浆内和细胞膜上 ;RT PCR方法可检测到HGF及其受体c MetmRNA的表达。结论 :人RPE细胞自身产生HGF并表达其受体c Met,提示HGF可能通过自分泌和 (或 )旁分泌途径作用于RPE细胞 ,涉及眼内多种疾病过程。

HGF/c-Met信号通路调控生殖细胞发生的研究进展

肝细胞生长因子(hepatocyte growth factor,HGF)为间质来源多效性生长因子,与肝细胞生长因子受体(HGF?receptor,也称c?Met)相结合,形成具有广泛生物学功能的HGF/c?Met信号通路,可促进细胞有丝分裂、生长、成熟、运动、组织形成过程以及诱导血管生成。以往研究表明HGF广泛表达于哺乳动物的睾丸和卵巢组织中,HGF/c?Met信号通路可参与调控卵泡发生和精子发生。本综述主要对近年HGF/c?Met信号通路对卵泡发生、精子发生的调控作用的研究进展进行概括。