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1.
Genes Cells ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136356

RESUMO

Identifying specific markers of adipose stem and progenitor cells (ASPCs) in vivo is crucial for understanding the biology of white adipose tissues (WAT). PDGFRα-positive perivascular stromal cells represent the best candidates for ASPCs. This cell lineage differentiates into myofibroblasts that contribute to the impairment of WAT function. However, ASPC marker protein(s) that are functionally crucial for maintaining WAT homeostasis are unknown. We previously identified Meflin as a marker of mesenchymal stem cells (MSCs) in bone marrow and tissue-resident perivascular fibroblasts in various tissues. We also demonstrated that Meflin maintains the undifferentiated status of MSCs/fibroblasts. Here, we show that Meflin is expressed in WAT ASPCs. A lineage-tracing experiment showed that Meflin+ ASPCs proliferate in the WAT of obese mice induced by a high-fat diet (HFD), while some of them differentiate into myofibroblasts or mature adipocytes. Meflin knockout mice fed an HFD exhibited a significant fibrotic response as well as increases in adipocyte cell size and the number of crown-like structures in WAT, accompanied by impaired glucose tolerance. These data suggested that Meflin expressed by ASPCs may have a role in reducing disease progression associated with WAT dysfunction.

2.
J Pathol ; 262(1): 61-75, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796386

RESUMO

Pancreatic stellate cells (PSCs) are stromal cells in the pancreas that play an important role in pancreatic pathology. In chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC), PSCs are known to get activated to form myofibroblasts or cancer-associated fibroblasts (CAFs) that promote stromal fibroinflammatory reactions. However, previous studies on PSCs were mainly based on the findings obtained using ex vivo expanded PSCs, with few studies that addressed the significance of in situ tissue-resident PSCs using animal models. Their contributions to fibrotic reactions in CP and PDAC are also lesser-known. These limitations in our understanding of PSC biology have been attributed to the lack of specific molecular markers of PSCs. Herein, we established Meflin (Islr), a glycosylphosphatidylinositol-anchored membrane protein, as a PSC-specific marker in both mouse and human by using human pancreatic tissue samples and Meflin reporter mice. Meflin-positive (Meflin+ ) cells contain lipid droplets and express the conventional PSC marker Desmin in normal mouse pancreas, with some cells also positive for Gli1, the marker of pancreatic tissue-resident fibroblasts. Three-dimensional analysis of the cleared pancreas of Meflin reporter mice showed that Meflin+ PSCs have long and thin cytoplasmic protrusions, and are localised on the abluminal side of vessels in the normal pancreas. Lineage tracing experiments revealed that Meflin+ PSCs constitute one of the origins of fibroblasts and CAFs in CP and PDAC, respectively. In these diseases, Meflin+ PSC-derived fibroblasts showed a distinctive morphology and distribution from Meflin+ PSCs in the normal pancreas. Furthermore, we showed that the genetic depletion of Meflin+ PSCs accelerated fibrosis and attenuated epithelial regeneration and stromal R-spondin 3 expression, thereby implying that Meflin+ PSCs and their lineage cells may support tissue recovery and Wnt/R-spondin signalling after pancreatic injury and PDAC development. Together, these data indicate that Meflin may be a marker specific to tissue-resident PSCs and useful for studying their biology in both health and disease. © 2023 The Pathological Society of Great Britain and Ireland.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pancreatite Crônica , Animais , Humanos , Camundongos , Carcinoma Ductal Pancreático/patologia , Fibrose , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Células Estreladas do Pâncreas/patologia , Pancreatite Crônica/genética , Pancreatite Crônica/metabolismo , Pancreatite Crônica/patologia , Regeneração
3.
Asian J Endosc Surg ; 10(4): 446-449, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28349649

RESUMO

A 60-year old woman had been hospitalized in a psychiatric hospital for 40 years for schizophrenia. An X-ray was performed when she fell, which showed needles in the abdominal field. After additional examinations and questioning, the patient was diagnosed with needles in the abdominal cavity, which were assumed to have been ingested and to have perforated the GI tract 40 years ago. They were removed by laparoscopic surgery. The needles were found in the omentum and near the left ovary. There were no inflammatory reactions around them. There have been previous reports about the removal of intra-abdominal foreign bodies, but foreign body reaction occurred in most of the reports. Our case had the longest period from ingestion of the foreign bodies to their removal. Laparoscopy and intraoperative fluoroscopy are useful for removing intra-abdominal foreign bodies because of their ability to help discriminate between structures and to navigate in real time.


Assuntos
Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Trato Gastrointestinal , Laparoscopia , Agulhas , Feminino , Corpos Estranhos/etiologia , Humanos , Pessoa de Meia-Idade , Fatores de Tempo , Tomografia Computadorizada por Raios X
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