Author: Yoshioka, Kosuke ; Ogasawara, Reiki ; Takahashi, Shuichiro ; Ara, Takahide ; Teshima, Takanori ; Hayase, Eiko ; Ohigashi, Hiroyuki ; Ebata, Ko ; Saito, Yumika ; Yamakawa, Tomohiro ; Yokoyama, Emi ; Hasegawa, Yuta ; Tomizuka, Kazuma

AbstractGraft-versus-host disease (GVHD) is the major obstacle to performing allogeneic hematopoietic cell transplantation (allo-HCT). We and others have shown that intestinal stem cells are targeted in lower gastrointestinal GVHD. A leucine-rich repeat–containing G-protein coupled receptor 5 (Lgr5)–expressing gastric stem cells (GSCs) reside at the base of the gastric glands in mice. After experimental allo-HCT, Lgr5+ GSCs significantly decreased. Parietal cells, which underwent continuous renewal by GSCs, were injured in gastric GVHD, leading to failure of gastric acidification and aerobic bacterial overgrowth in the duodenum. Fate-mapping analysis demonstrated that administration of R-Spondin1 (R-Spo1) that binds to Lgr5 for 6 days in naïve mice significantly increased proliferating epithelial cells derived from Lgr5+ GSCs. R-Spo1 administered on days −3 to −1 and from days +1 to +3 of allo-HCT protected GSCs, leading to amelioration of gastric GVHD and restoration of gastric acidification, and suppression of aerobic bacterial overgrowth in the duodenum. In conclusion, Lgr5+ GSCs were targeted by gastric GVHD, resulting in disruption of the gastric homeostasis, whereas R-Spo1 protected Lgr5+ GSCs from GVHD and maintained homeostasis in the stomach.

20 Jul 2023·Acta biochimica et biophysica Sinica

Novel recombinant R-spondin1 promotes hair regeneration by targeting the Wnt/β-catenin signaling pathway.

Article

Author: Liu, Zejian ; Chen, Zefeng ; Wang, Xiuqi ; Feng, Jiaxin ; Lu, Zhujin ; Chen, Yijun ; Yan, Huichao ; Gao, Chunqi

Roof plate-specific spondin 1 (R-spondin1, RSPO1) is a Wnt/β-catenin signaling pathway activator that binds with Wnt ligands to stimulate the Wnt/β-catenin signaling pathway, which is key to hair regeneration. However, it is not clear whether recombinant RSPO1 (rRSPO1) affects hair regeneration. Here, we treat C57BL/6 male mice with rRSPO1 and investigate the expression of the Wnt/β-catenin signaling pathway and the activation of hair follicle stem cells in the dorsal skin. The mouse skin color score and hair-covered area are determined to describe hair growth, and the skin samples are subjected to H&E staining, western blot analysis and immunofluorescence staining to evaluate hair follicle development and the expressions of Wnt/β-catenin signaling pathway-related proteins. We find that rRSPO1 activates mouse hair follicle stem cells (mHFSCs) and accelerates hair regeneration. rRSPO1 increases the hair-covered area, the number of hair follicles, and the hair follicle diameter and length. Moreover, rRSPO1 enhances the activity of Wnt/β-catenin signaling pathway-related proteins and the expressions of HFSC markers, as well as mHFSC viability. These results indicate that subcutaneous injection of rRSPO1 can improve hair follicle development by activating the Wnt/β-catenin signaling pathway, thereby promoting hair regeneration. This study demonstrates that rRSPO1 has the potential to treat hair loss by activating the Wnt/β-catenin signaling pathway.

31 Aug 2022·Journal of Agricultural and Food Chemistry

Recombinant Porcine R-Spondin 1 Facilitates Intestinal Stem Cell Expansion along the Crypt–Villus Axis through Potentiating Wnt/β-Catenin Signaling in Homeostasis and Deoxynivalenol Injury

Article

Author: Wang, Xiu-qi ; Gao, Chun-qi ; Zhou, Jia-yi ; Zhu, Qiu-jie ; Zan, Geng-xiu ; Yan, Hui-chao

R-spondin 1 (RSPO1) is a ligand for the intestinal stem cell (ISC) marker Lgr5 in the crypt, which functions to amplify canonical Wnt signaling to stimulate the division of ISCs. Despite the crucial role of recombinant human RSPO1 (rhRSPO1) in homeostasis and regeneration, little is known about RSPO1 among different species. Here, we cloned the porcine RSPO1 (pRSPO1) gene and obtained rpRSPO1 protein through the expression system of the recombinant Escherichia coli Rosetta (DE3) chemical competent cells. Using the in vitro IPEC-J2 model that combines cell proliferation evaluation approaches, we identified the rpRSPO1 activity in stimulating jejunal epithelial cells. And upon deoxynivalenol challenge in mice, we found that rpRSPO1 ameliorated their growth retardation and jejunal epithelial integrity. Importantly, the ISCs in the jejunum had greater proliferation and differentiation potential that was accompanied by Wnt/β-catenin pathway activation after rpRSPO1 modulation. Subsequently, the jejunal organoids expanded from these ISCs ex vivo presented robust growth advantages. And the rpRSPO1 was able to guide Wnt/β-catenin activity to increase ISC activity. Our work systematically demonstrates that rpRSPO1 facilitates ISC expansion by potentiating Wnt/β-catenin signaling during homeostasis and responding to deoxynivalenol perturbations.

100 Deals associated with Recombinant human R-spondin 1(ARCA biopharma)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Bone Diseases	Phase 1	-	Kyowa Kirin Co., Ltd.	-
Bone Diseases	Phase 1	Australia	-	-
Bone Diseases	Phase 1	China	ARCA biopharma, Inc.	-
Inflammatory Bowel Diseases	Phase 1	Australia	-	-
Inflammatory Bowel Diseases	Phase 1	-	Kyowa Kirin Co., Ltd.	-
Inflammatory Bowel Diseases	Phase 1	China	ARCA biopharma, Inc.	-
Mucositis	Phase 1	-	Kyowa Kirin Co., Ltd.	-
Mucositis	Phase 1	China	ARCA biopharma, Inc.	-
Mucositis	Phase 1	Australia	-	-
Wounds and Injuries	Phase 1	Australia	-	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

Recombinant human R-spondin 1(ARCA biopharma)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation