scholarly journals Hepatocyte growth factor as a hematopoietic regulator

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3093-3100 ◽  
Author(s):  
T Nishino ◽  
H Hisha ◽  
N Nishino ◽  
M Adachi ◽  
S Ikehara
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Fetal Liver ◽  
Fetal Life ◽  
Cell Counts ◽  
Proliferation And Differentiation ◽  
Nonadherent Cell ◽  
Hepatocyte Growth ◽  
Synergistic Increase

Hepatocyte growth factor (HGF) was originally isolated as a mitogen for adult hepatocytes, but this cytokine is now regarded as a multi-functional factor. In the present study, we show that the mouse liver in the middle and/or late stage of the fetal life expresses both HGF and c-met (its receptor) messages. HGF and c-met mRNA are coexpressed not only in the adherent layers of fetal liver long-term cultures (FL-LTCs) and adult bone marrow long-term cultures (BM-LTCs), but also in the stromal cell lines MS-5 and PA-6. Addition of human HGF (2 and 20 ng/mL) to the LTCs enhances (1) nonadherent cell counts (ninefold in FL-LTCs and sixfold in BM-LTCs), (2) nonadherent colony-forming unit-in culture (CFU-C) counts (eightfold in FL-LTCs and fivefold in BM-LTC), and (3) cobblestone colony counts. However, HGF slightly inhibits the proliferation of stromal cells. No direct effect of HGF on freshly isolated BM and/or FL cells is found in the CFU-C assay. However, an approximately 1.5-fold synergistic increase in CFU-C counts is noted when the BM or FL cells are cocultured with HGF in the presence of interleukin-3. These findings strongly suggest that HGF plays a crucial role as a hematopoietic regulator in the proliferation and differentiation of hematopoietic progenitors.

scholarly journals A Potential Mechanism of Tumor Progression during Systemic Infections Via the Hepatocyte Growth Factor (HGF)/c-Met Signaling Pathway

2020 ◽  
Vol 9 (7) ◽  
pp. 2074 ◽  
Author(s):  
Hironori Tsujimoto ◽  
Hiroyuki Horiguchi ◽  
Yusuke Matsumoto ◽  
Risa Takahata ◽  
Nariyoshi Shinomiya ◽  
...  
Keyword(s):  
Growth Factor ◽  
Liver Metastasis ◽  
Hepatocyte Growth Factor ◽  
Liver Metastases ◽  
Signaling Pathway ◽  
Tumor Cells ◽  
High Serum ◽  
Term Survival ◽  
Hepatocyte Growth

Background: Increasing evidence has demonstrated that postoperative infectious complications (PICs) after digestive surgery are significantly associated with negative long-term outcomes; however, precise mechanisms of how PICs affect the poor long-term survival remain unclear. Here, we focused on the hepatocyte growth factor (HGF)/c-Met signaling pathway as one of those mechanisms. Methods: In the clinical setting, serum HGF levels were measured in the patients with sepsis and those with PICs after undergoing esophagectomy. Using a liver metastasis mouse model with cecal ligation and puncture (CLP), expressions of HGF and the roles of the HGF/c-Met pathway in the progression of tumor cells were examined. Results: Serum HGF levels were very high in the patients with intra-abdominal infection on postoperative days (PODs) 1, 3, and 5; similarly, compared to the patients without PICs, those with PICs had significantly higher serum HGF levels on 1, 3, and 5 days after esophagectomy. The patients with PICs showed poorer overall survival than those without PICs, and the patients with high serum HGF levels on POD 3 showed poorer prognosis than those with low HGF levels. Similarly, at 24 and 72 h after operation, serum levels of HGF in CLP mice were significantly higher than those in sham-operated mice. Intraperitoneal injection of mouse recombinant HGF significantly promoted liver metastases in sham-operated mice on 14 days after surgery. Knocking down c-Met expression on NL17 tumor cells by RNAi technology significantly inhibited the promotion of CLP-induced liver metastases. Conclusions: Infections after surgery increased serum HGF levels in the clinical as well as experimental settings. Induction of high serum HGF levels by CLP promoted liver metastases in a murine liver metastasis model, suggesting the involvement of the HGF/c-Met signaling pathway in tumor promotion mechanisms. Thus, targeting the HGF/c-Met signaling pathway may be a promising approach for malignant tumors, particularly in the patients with PICs.

scholarly journals Long-term effects of hepatocyte growth factor gene therapy in rat myocardial infarct model

Gene Therapy ◽  
2011 ◽  
Vol 19 (8) ◽  
pp. 836-843 ◽  
Author(s):  
Y-N Jin ◽  
M Inubushi ◽  
K Masamoto ◽  
K Odaka ◽  
I Aoki ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Myocardial Infarct ◽  
Long Term Effects ◽  
Factor Gene ◽  
Growth Factor Gene ◽  
Myocardial Infarct Model ◽  
Hepatocyte Growth

scholarly journals Hepatocyte growth factor regulates the proliferation and differentiation of cartilage in developing forelimb of mouse embryos in vitro

2004 ◽  
Vol 25 (5) ◽  
pp. 219-227 ◽  
Author(s):  
Ayumu KOBAYASHI ◽  
Osamu AMANO ◽  
Yuji TANI ◽  
Toshikazu NAKAMURA ◽  
Shoichi ISEKI ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Mouse Embryos ◽  
Proliferation And Differentiation ◽  
Hepatocyte Growth

scholarly journals Progress of Gene Therapy in Cardiovascular Disease

Hypertension ◽  
2020 ◽  
Vol 76 (4) ◽  
pp. 1038-1044
Author(s):  
Munehisa Shimamura ◽  
Hironori Nakagami ◽  
Fumihiro Sanada ◽  
Ryuichi Morishita
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Dna Vaccine ◽  
Critical Limb Ischemia ◽  
Dna Vaccines ◽  
Limb Ischemia ◽  
Hepatocyte Growth

Gene therapy has been extensively studied in peripheral and cardiac ischemia, heart and vein graft failure, and dyslipidemia, but most clinical trials failed to show their efficacies despite good outcomes in preclinical studies. So far, 2 gene therapies for dyslipidemia and one for critical limb ischemia in peripheral artery disease have been approved. In critical limb ischemia, gene therapy using proangiogenic factors has emerged as a novel therapeutic modality for promoting angiogenesis. Initial researches mainly focused on vascular endothelial growth factor, fibroblast growth factor, or hepatocyte growth factor. After the favorable results of basic research, several phase I and II clinical trials of these proangiogenic factors have shown promising results. However, only a phase III clinical trial of the intramuscular injection of hepatocyte growth factor plasmid DNA has shown successful outcomes, and it was recently approved in Japan for treating patients with critical limb ischemia who have ulcers and for whom no alternative therapeutic options are available. DNA vaccine is another promising modality of gene therapy. An antitumor vaccine suppressing angiogenesis through the inhibition of proangiogenic factors and an antihypertensive vaccine inhibiting the renin–angiotensin system are representative DNA vaccines. The advantage of DNA vaccine is its long-term effectiveness with a few vaccinations; however, the benefits and risks, such as adverse T-cell reaction against self-antigen or long-term side effects, of DNA vaccines should be carefully evaluated. In this review, we discuss the recent advances in proangiogenic gene therapy for critical limb ischemia and DNA vaccine for hypertension.

Intestinal fibroblasts regulate intestinal epithelial cell proliferation via hepatocyte growth factor

1998 ◽  
Vol 274 (5) ◽  
pp. G809-G818 ◽  
Author(s):  
Michael Göke ◽  
Michiyuki Kanai ◽  
Daniel K. Podolsky
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Epithelial Cell ◽  
Hepatocyte Growth Factor ◽  
Protein Expression ◽  
Conditioned Medium ◽  
Intestinal Epithelial Cell ◽  
Intestinal Epithelial ◽  
Cell Counts ◽  
Hepatocyte Growth

Although the presence of subepithelial intestinal fibroblasts has been well recognized, the effects of fibroblasts on intestinal epithelial cell (IEC) growth are incompletely understood. In vitro studies were undertaken to evaluate the effects of fibroblasts on the proliferation of model IEC lines. IECs (Caco-2, T84, and IEC-6) were grown alone or in the presence of human intestinal (CCD-18), lung (CCD-37), or skin explant-derived fibroblasts. Cocultures were carried out directly on irradiated fibroblasts or by Transwell coculture technique with fibroblasts and epithelial cells separated by a porous filter. Cell proliferation was assessed by [3H]thymidine incorporation and cell counts. Hepatocyte growth factor (HGF) and c- met transcript expression in IECs and fibroblasts was examined by RT-PCR and Northern blotting; protein expression was evaluated by immunoblotting. Intestinal as well as lung and skin fibroblasts substantially stimulated proliferation of Caco-2, T84, and IEC-6 cells in both direct and Transwell cocultures. In addition, fibroblast-conditioned medium stimulated IEC proliferation, suggesting a paracrine mechanism. Anti-human HGF-neutralizing antibodies blocked the growth-promoting effects in both fibroblasts and fibroblast-conditioned medium. Recombinant human HGF dose dependently promoted IEC proliferation. HGF mRNA and protein expression was restricted to fibroblasts. High levels of c- met expression were found in Caco-2 and T84 cells; in contrast, expression in fibroblasts was weak. In summary, fibroblasts stimulate IEC proliferation through a paracrine mechanism mediated predominantly by HGF.

scholarly journals Ovulation sources coagulation protease cascade and hepatocyte growth factor to support physiological growth and malignant transformation

2021 ◽  
Author(s):  
Hsuan-Shun Huang ◽  
Pao-Chu Chen ◽  
Sung-Chao Chu ◽  
Ming-Hsun Lee ◽  
Chi-Ya Huang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Malignant Transformation ◽  
Blood Circulation ◽  
Tissue Injury ◽  
Serous Carcinoma ◽  
Transient Event ◽  
Transformation Activity ◽  
Hepatocyte Growth

The fallopian tube fimbrial epithelium (FTE), which is exposed to the follicular fluid (FF) contents of ovulation, is regarded as the main origin of ovarian high-grade serous carcinoma (HGSC). Previously, we found that growth factors in FF, such as IGF2, are responsible for the malignant transformation of FTE. However, ovulation is a monthly transient event, whereas carcinogenesis requires continuous, long-term exposure. Here, we found the transformation activity of FF sustained for more than 30 days after drainage into the peritoneal fluid (PF). Hepatocyte growth factor (HGF), activated through the ovulation injury-tissue factor-thrombin-HGFA-HGF cleavage cascade confers a sustained transformation activity to FTE, HGSC. Physiologically, the high reserve of the coagulation-HGF cascade sources a sustained level of HGF in PF, then to the blood circulation. This HGF axis promotes the growth of the corpus luteum and repair of tissue injury after ovulation.

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