Paired box-4 (PAX4) and aristaless-related homebox (ARX) are two transcription factors involved in the development of endocrine pancreas in humans. PAX4 and ARX are responsible for the development of β-cells and α-cells respectively. In adulthood PAX4 contributes to reprogramming of exocrine into endocrine cells and α-cells into β-cells; the induction of ARX in β-cells leads to reprogramming into α-cells. Information is not available in diabetic cats. The study aim was to verify if diabetic cats have increased number of pancreatic cells expressing developmental markers of α- and β-cells, suggesting reprogramming. The research was based on pancreatic tissue samples from 18 cats, 9 were diabetic cats and 9 were well-matched control cats. The collected tissues were fixed in formalin, embedded in paraffin and sectioned. Tissue sections were labelled for insulin, glucagon, PAX4 and ARX. The number of positive-cells for each marker and double-positive for their combinations was counted in the pancreas and compared between groups. Compared to controls, diabetic cats had less insulin-positive cells in the islet and exocrine pancreas (p = 0.001, p = 0.038); no differences were found in the number of glucagon-positive cells. In the endocrine pancreas, diabetic cats had more insulin/glucagon-positive cells (p = 0.024), PAX4-positive cells (p = 0.038) and PAX4/insulin-positive cells (p = 0.027). In the exocrine pancreas, diabetic cats had less ARX/glucagon-positive cells (p = 0.029). In conclusion, the increased number of islet cells expressing PAX4 in diabetic cats suggests that β-cells may change to an earlier stage of differentiation or new β-cells are formed. Moreover, the increased number of islet insulin/glucagon-positive cells may indicate that α-cells are transforming into β-cells or vice versa. Hence, reprogramming occurs in diabetic cats, specifically in the islets. The reason behind the lower count of cells concurrently expressing ARX and glucagon in the exocrine pancreas of diabetic cats is unclear.
I fattori di trascrizione sono responsabili dello sviluppo del pancreas endocrino negli umani. In particolare, i geni paired box-4 (PAX4) e aristaless-related homeobox (ARX) codificano per le omonime proteine, che fungono da fattori di trascrizione coinvolti rispettivamente nello sviluppo delle cellule β e α. Si è visto che, in età adulta, PAX4 contribuisce alla riprogrammazione delle cellule α in cellule β, ma anche delle cellule esocrine in cellule endocrine. Invece, l’induzione di ARX porta alla riprogrammazione delle cellule β in cellule α. Per quanto riguarda il gatto, non esistono informazioni di questo tipo. L’obiettivo dello studio, quindi, era di verificare se i gatti diabetici presentavano un maggior numero di cellule pancreatiche in grado di esprimere i marcatori di sviluppo delle cellule α e β, suggerendo una possibile riprogrammazione delle cellule stesse. La ricerca si è basata su campioni di tessuto pancreatico proveniente da 18 gatti, di cui 9 diabetici e 9 che fungevano da controllo. Il tessuto prelevato è stato fissato in formalina, incluso in paraffina e sezionato. In ogni sezione è stata valutata la presenza di insulina, glucagone, PAX4, ARX e delle diverse combinazioni degli stessi. Sono state conteggiate le cellule risultate positive o doppiamente positive per i marcatori precedentemente elencati ed è stato eseguito un confronto tra gatti diabetici e controlli. Rispetto ai controlli, i gatti diabetici presentavano un minor numero di cellule positive per l’insulina all’interno delle isole pancreatiche (p=0.001 vs p=0.038), mentre non differiva il numero di cellule positive per il glucagone. A livello di pancreas endocrino, i gatti diabetici mostravano un maggior numero di cellule positive per la combinazione insulina e glucagone (p=0.024), per la proteina PAX4 (p=0.038) e per la combinazione PAX4 e insulina (p=0.027). Infine, per quanto concerne il pancreas esocrino, i gatti diabetici presentavano un aumento del numero di cellule positive contemporaneamente per ARX e glucagone (p=0.029). In conclusione, l’aumento delle cellule che esprimono PAX4 suggerisce che le cellule β presenti nel pancreas endocrino dei gatti diabetici siano in grado di rigenerarsi o di passare ad un precedente stadio di differenziazione. Inoltre, l’aumento del numero di cellule positive sia per insulina che per glucagone può indicare una possibile riprogrammazione delle cellule α in β o viceversa. È stato dunque provato che nei gatti diabetici avviene una riprogrammazione delle cellule pancreatiche, soprattutto nel pancreas endocrino. Il motivo alla base dell’aumento delle cellule positive per ARX e glucagone nei gatti diabetici non è chiaro.
Riprogrammazione del pancreas endocrino nei gatti diabetici
ZANON, ALICE
2021/2022
Abstract
Paired box-4 (PAX4) and aristaless-related homebox (ARX) are two transcription factors involved in the development of endocrine pancreas in humans. PAX4 and ARX are responsible for the development of β-cells and α-cells respectively. In adulthood PAX4 contributes to reprogramming of exocrine into endocrine cells and α-cells into β-cells; the induction of ARX in β-cells leads to reprogramming into α-cells. Information is not available in diabetic cats. The study aim was to verify if diabetic cats have increased number of pancreatic cells expressing developmental markers of α- and β-cells, suggesting reprogramming. The research was based on pancreatic tissue samples from 18 cats, 9 were diabetic cats and 9 were well-matched control cats. The collected tissues were fixed in formalin, embedded in paraffin and sectioned. Tissue sections were labelled for insulin, glucagon, PAX4 and ARX. The number of positive-cells for each marker and double-positive for their combinations was counted in the pancreas and compared between groups. Compared to controls, diabetic cats had less insulin-positive cells in the islet and exocrine pancreas (p = 0.001, p = 0.038); no differences were found in the number of glucagon-positive cells. In the endocrine pancreas, diabetic cats had more insulin/glucagon-positive cells (p = 0.024), PAX4-positive cells (p = 0.038) and PAX4/insulin-positive cells (p = 0.027). In the exocrine pancreas, diabetic cats had less ARX/glucagon-positive cells (p = 0.029). In conclusion, the increased number of islet cells expressing PAX4 in diabetic cats suggests that β-cells may change to an earlier stage of differentiation or new β-cells are formed. Moreover, the increased number of islet insulin/glucagon-positive cells may indicate that α-cells are transforming into β-cells or vice versa. Hence, reprogramming occurs in diabetic cats, specifically in the islets. The reason behind the lower count of cells concurrently expressing ARX and glucagon in the exocrine pancreas of diabetic cats is unclear.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/34614