scholarly journals Distinct Localization of Mature HGF from its Precursor Form in Developing and Repairing the Stomach

2019 ◽  
Vol 20 (12) ◽  
pp. 2955 ◽  
Author(s):  
Nawaphat Jangphattananont ◽  
Hiroki Sato ◽  
Ryu Imamura ◽  
Katsuya Sakai ◽  
Yumi Terakado ◽  
...  

Hepatocyte growth factor (HGF) is secreted as an inactive single-chain HGF (scHGF); however, only proteolytically processed two-chain HGF (tcHGF) can activate the MET receptor. We investigated the localization of tcHGF and activated/phosphorylated MET (pMET) using a tcHGF-specific antibody. In day 16.5 mouse embryos, total HGF (scHGF + tcHGF) was mainly localized in smooth muscle cells close to, but separate from, MET-positive epithelial cells in endodermal organs, including the stomach. In the adult stomach, total HGF was localized in smooth muscle cells, and tcHGF was mainly localized in the glandular base region. Immunostaining for pMET and Lgr5-driven green fluorescent protein (GFP) indicated that pMET localization overlapped with Lgr5+ gastric stem cells. HGF promoted organoid formation similar to EGF, indicating the potential for HGF to promote the survival and growth of gastric stem cells. pMET and tcHGF localizations changed during regeneration following gastric injury. These results indicate that MET is constantly activated in gastric stem cells and that the localization of pMET differs from the primary localization of precursor HGF but has a close relationship to tcHGF. Our results suggest the importance of the microenvironmental generation of tcHGF in the regulation of development, regeneration, and stem cell behavior.

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 792
Author(s):  
Xixiang Gao ◽  
Mingjie Gao ◽  
Jolanta Gorecka ◽  
John Langford ◽  
Jia Liu ◽  
...  

Induced pluripotent stem cells (iPSC) represent an innovative, somatic cell-derived, easily obtained and renewable stem cell source without considerable ethical issues. iPSC and their derived cells may have enhanced therapeutic and translational potential compared with other stem cells. We previously showed that human iPSC-derived smooth muscle cells (hiPSC-SMC) promote angiogenesis and wound healing. Accordingly, we hypothesized that hiPSC-SMC may be a novel treatment for human patients with chronic limb-threatening ischemia who have no standard options for therapy. We determined the angiogenic potential of hiPSC-SMC in a murine hindlimb ischemia model. hiPSC-SMC were injected intramuscularly into nude mice after creation of hindlimb ischemia. Functional outcomes and perfusion were measured using standardized scores, laser Doppler imaging, microCT, histology and immunofluorescence. Functional outcomes and blood flow were improved in hiPSC-SMC-treated mice compared with controls (Tarlov score, p < 0.05; Faber score, p < 0.05; flow, p = 0.054). hiPSC-SMC-treated mice showed fewer gastrocnemius fibers (p < 0.0001), increased fiber area (p < 0.0001), and enhanced capillary density (p < 0.01); microCT showed more arterioles (<96 μm). hiPSC-SMC treatment was associated with fewer numbers of macrophages, decreased numbers of M1-type (p < 0.05) and increased numbers of M2-type macrophages (p < 0.0001). Vascular endothelial growth factor (VEGF) expression in ischemic limbs was significantly elevated with hiPSC-SMC treatment (p < 0.05), and inhibition of VEGFR-2 with SU5416 was associated with fewer capillaries in hiPSC-SMC-treated limbs (p < 0.0001). hiPSC-SMC promote VEGF-mediated angiogenesis, leading to improved hindlimb ischemia. Stem cell therapy using iPSC-derived cells may represent a novel and potentially translatable therapy for limb-threatening ischemia.


2017 ◽  
Vol 15 (6) ◽  
pp. 3787-3795 ◽  
Author(s):  
Kaisaier Aji ◽  
Yun Zhang ◽  
Abudusaimi Aimaiti ◽  
Yujie Wang ◽  
Mulati Rexiati ◽  
...  

2021 ◽  
Vol 16 (2) ◽  
pp. 025016
Author(s):  
Martina Travnickova ◽  
Nikola Slepickova Kasalkova ◽  
Antonin Sedlar ◽  
Martin Molitor ◽  
Jana Musilkova ◽  
...  

2017 ◽  
Vol 70 (16) ◽  
pp. C70
Author(s):  
Chengfei Peng ◽  
Xiaoping Shao ◽  
Xiaoxiang Tian ◽  
Chenghui Yan ◽  
Yaling Han ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document