PXD059561
PXD059561 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Local growth hormone facilitates the aging colon epithelial microenvironment |
| Description | Aging is associated with appearance of senescent cells secreting the senescence-associated secretome facilitating a milieu favoring age-related changes in microenvironment. Previously, we showed accumulation and secretion of local non-pituitary growth hormone (npGH) in senescent colon epithelial cells. Here, we elucidate mechanisms underlying npGH action in the non-tumorous colon tissue microenvironment. We demonstrate autocrine npGH action in normal human colon cells (hNCC) infected with lentivirus expressing hGH (lentiGH), as well as paracrine npGH action in hNCC cocultured with lentiGH hNCC and in intact human 3-dimensional intestinal organoids co-cultured with organoids infected with lentiGH. Enriched gene ontology and pathway analysis of intact organoids exposed to paracrine npGH identified distorted extracellular matrix (ECM) and focal adhesion pathways concurrent with altered expression of ECM and cytoskeletal proteins. Significant phosphoprotein changes associated with cytoskeleton and cell migration pathway occurred in GH-exposed hNCC. Paracrine npGH triggers these changes by activating epithelial-mesenchymal transition, as shown by suppression of E-cadherin and induction of Twist2 in cellular models, as well as in the colon of nude mice harboring GH-secreting xenografts. These changes are consistent with observed increased migration of hNCC overexpressing lentiGH, or in those co-cultured with GH-secreting hNCC or with GH-secreting normal colon fibroblasts. Furthermore, whole exome sequencing detected increased cell copy number alterations in intact organoids co-cultured with lentiGH-infected organoids, likely as a consequence of GH-mediated suppressed DNA damage repair thereby favoring cell transformation. Our results indicate that accumulated npGH in aging tissue enables a microenvironment landscape favoring age-associated pro-proliferative changes. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-07-29 |
| AnnouncementXML | Submission_2025-07-29_14:15:09.995.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Arminja Nadine Kettenbach |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Phospho |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-01-08 13:56:26 | ID requested | |
| ⏵ 1 | 2025-07-29 14:15:10 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Growth hormone, aging, extracellular matrix, epithelial-mesenchymal transition, DatasetType:Proteomics |
Contact List
| Arminja Kettenbach | |
|---|---|
| contact affiliation | Geisel School of Medicine at Dartmouth College |
| contact email | arminja.n.kettenbach@dartmouth.edu |
| lab head | |
| Arminja Nadine Kettenbach | |
| contact affiliation | Dartmouth |
| contact email | Arminja.N.Kettenbach@Dartmouth.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v06/MSV000096807/ |
to receive all new ProteomeXchange dataset release announcements!
