{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that noncoding RNAs derived from the pregnancy‐associated plasma protein A (PAPPA) locus play important regulatory roles in human disease. For example, the circular RNA version of PAPPA (circPAPPA) was found to be down‐regulated in preeclampsia, with reduced expression leading to impaired trophoblast proliferation and invasion via modulation of the miR‐384/STAT3 signaling pathway. Although this work focused on circPAPPA, it highlights the broader concept that PAPPA‐related RNAs are key modulators of cell function in pathologic conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a distinct yet related context, the long noncoding RNA PAPPA-AS1 has been implicated in the development of hypertrophic scars. PAPPA-AS1 is significantly upregulated in hypertrophic scar tissues and fibroblasts, where it appears to promote fibrosis by enhancing the Toll-like receptor 4 (TLR4) signaling cascade. Mechanistically, PAPPA-AS1 interacts with the RNA-binding protein TAF15, thereby upregulating TLR4 expression, which in turn increases downstream fibrotic mediators such as TGF-β1, collagen I/III, and α-SMA. Knockdown of PAPPA-AS1 resulted in reduced fibroblast proliferation and diminished expression of these fibrosis markers, indicating its potential as a therapeutic target in wound repair and scarring."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wenbo Zhou, Huiyan Wang, Jingjing Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulated circPAPPA suppresses the proliferation and invasion of trophoblast cells via the miR-384/STAT3 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20191965"}], "href": "https://doi.org/10.1042/BSR20191965"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31427481"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31427481"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Pengju Fan, Yongjie Wang, Jingjing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "lncRNA PAPPA-AS1 Induces the Development of Hypertrophic Scar by Upregulating TLR4 through Interacting with TAF15."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mediators Inflamm (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/3170261"}], "href": "https://doi.org/10.1155/2021/3170261"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34285657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34285657"}]}]}]}