R-Spondin 3 Proteins (RSPO3)

Human R-Spondin 3 (RSPO3) interaction partners

1. Knockdown of RSPO3 resulted in significantly increased mRNA expression levels of RUNX2 (show RUNX2 Proteins), ALP (show ALP Proteins) and OCN and no effects on the proliferation of human adipose-derived stem cells.

2. For liver transplant-free survival, a genome-wide significant signal was identified and expression of the candidate gene RSPO3 was demonstrated in key liver-resident effector cells and may play a role in primary sclerosing cholangitis disease progression.

3. The present study identified RSPO (show RSPO1 Proteins) fusion transcripts, including three novel transcripts, in one-third of colorectal Traditional serrated adenoma (TSA (show PRDX2 Proteins)) and showed that PTPRK (show PTPRK Proteins)-RSPO3 fusions were the predominant cause of RSPO (show RSPO1 Proteins) overexpression in colorectal TSA (show PRDX2 Proteins).

4. RSPOs facilitate HSC (show FUT1 Proteins) activation and promote liver fibrogenesis by enhancing the Wnt (show WNT2 Proteins) pathway

5. Colorectal cancer cell lines identified VACO6 cells as a carrier of a canonical PTPRK (show PTPRK Proteins)(e1)-RSPO3(e2) fusion; cell line displayed marked in vitro and in vivo sensitivity to WNT (show WNT2 Proteins) blockade by the porcupine (show PORCN Proteins) inhibitor LGK974. Long-term treatment of VACO6 cells with LGK974 led to the emergence of a resistant population carrying two frameshift deletions of the WNT (show WNT2 Proteins) pathway inhibitor AXIN1 (show AXIN1 Proteins), with consequent protein loss.

6. PTPRK (show PTPRK Proteins)-RSPO3 fusions and RNF43 (show RNF43 Proteins) mutations were found to be characteristic genetic features of traditional serrated adenomas (TSAs).

7. Using C-mannosylation-defective Rspo3 mutant-overexpressing cell lines, we found that C-mannosylation of Rspo3 promotes its secretion and activates Wnt (show WNT2 Proteins)/beta-catenin (show CTNNB1 Proteins) signaling.

8. High RSPO3 expression is associated with breast cancer.

9. A genome-wide association study of bone mineral density (BMD (show BEST1 Proteins)) found a new BMD (show BEST1 Proteins) locus that harbors the PTCH1 (show PTCH1 Proteins) gene, that associates with reduced spine BMD (show BEST1 Proteins) and the RSPO3 associates with increased spine BMD (show BEST1 Proteins).

10. results suggest that the expression of RSPO (show RSPO1 Proteins) fusion transcripts is related to a subset of colorectal cancers arising in the Japanese population

Mouse (Murine) R-Spondin 3 (RSPO3) interaction partners

1. These results shed new light on the role of Rspo3 in heart development and demonstrate that LGR4 (show LGR4 Proteins) is the principal R-spondin 3 receptor in the heart.

2. Results identify a mechanism through which localized expression of RSPO3 induces proliferation of the coronary arteries at their stems and permits their formation.

3. Rspo3-LGR4 (show LGR4 Proteins) axis protects hepatocytes from hypoxia/reoxygenation injury via activating beta-catenin (show CTNNB1 Proteins).

4. H. pylori infection increases stromal R-spondin 3 expression and expands the Axin2 (show AXIN2 Proteins)(+) cell pool to cause hyperproliferation and gland hyperplasia; the ability of stromal niche cells to control and adapt epithelial stem cell dynamics constitutes a sophisticated mechanism that orchestrates epithelial regeneration and maintenance of tissue integrity

5. We provide in vivo evidence that RSPO3 stimulates the crypt stem cell and niche compartments and drives rapid intestinal tumorigenesis.

6. Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa

7. Conditional deletion of Rspo3 in mice disrupts activation of central fate, demonstrating its crucial role in determining and maintaining beta-catenin (show CTNNB1 Proteins)-dependent zonation.

8. data identify endothelial RSPO3-driven non-canonical WNT (show WNT2 Proteins)/Ca(2 (show CA2 Proteins)+)/NFAT (show NFATC1 Proteins) signaling as a critical maintenance pathway of the remodeling vasculature

9. Nkx2-5 (show NKX2-5 Proteins) has a role in regulating cardiac growth through modulation of Wnt (show WNT2 Proteins) signaling by R-spondin3

10. Rspo3 loss of function mutation in combination with Rspo2 (show RSPO2 Proteins) mutation,but not on its own, causes severe limb truncation.