GATA4 induces liver fibrosis regression by deactivating hepatic stellate cells.

In response to liver injury, hepatic stellate cells activate and acquire proliferative and contractile features. The regression of liver fibrosis appears to involve the clearance of activated hepatic stellate cells, either by apoptosis or by reversion toward a quiescent-like state, a process called deactivation. Thus, deactivation of active hepatic stellate cells has emerged as a novel and promising therapeutic approach for liver fibrosis. However, our knowledge of the master regulators involved in the deactivation and/or activation of fibrotic hepatic stellate cells is still limited. The transcription factor GATA4 has been previously shown to play an important role in embryonic hepatic stellate cell quiescence. In this work, we show that lack of GATA4 in adult mice caused hepatic stellate cell activation and, consequently, liver fibrosis. During regression of liver fibrosis, Gata4 was reexpressed in deactivated hepatic stellate cells. Overexpression of Gata4 in hepatic stellate cells promoted liver fibrosis regression in CCl4-treated mice. GATA4 induced changes in the expression of fibrogenic and antifibrogenic genes, promoting hepatic stellate cell deactivation. Finally, we show that GATA4 directly repressed EPAS1 transcription in hepatic stellate cells and that stabilization of the HIF2α protein in hepatic stellate cells leads to liver fibrosis.

Loss of GATA4 causes ectopic pancreas in the stomach.

Pancreatic heterotopia is defined as pancreatic tissue outside its normal location in the body and anatomically separated from the pancreas. In this work we have analyzed the stomach glandular epithelium of Gata4 flox/flox ; Pdx1-Cre mice (Gata4KO mice). We found that Gata4KO glandular epithelium displays an atypical morphology similar to the cornified squamous epithelium and exhibits upregulation of forestomach markers. The developing gastric units fail to form properly, and the glandular epithelial cells do not express markers of gastric gland in the absence of GATA4. Of interest, the developing glands of the Gata4KO stomach express pancreatic cell markers. Furthermore, a mass of pancreatic tissue located in the subserosa of the Gata4KO stomach is observed at adult stages. Heterotopic pancreas found in Gata4-deficient mice contains all three pancreatic cell lineages: ductal, acinar, and endocrine. Moreover, Gata4 expression is downregulated in ectopic pancreatic tissue of some human biopsy samples. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Pilomatrix carcinoma: Reporte de un caso y revisión de la literatura / Pilomatrix carcinoma: Case report and literature review

Pilomatrix carcinoma es la forma maligna del pilomatrixoma que es una neoplasia benigna que se presenta en niños y adultos. Es infrecuente, se presenta como un nódulo solitario a predominio de cabeza y cuello, de tamaño variable; en varones de mediana edad. Se considera una neoplasia maligna de bajo grado y el manejo de elección es la escisión completa. Se presenta el caso de un varón de 32 años con un nódulo en región temporal occipital derecha, blando e indoloro, de 1,8 cm de longitud. Al corte se observó un tejido sólido amarillento encapsulado, y a la microscopía, bordes bien delimitados por células basaloides con núcleos hipercromáticos, pleomórficos, nucléolo prominente y de 0 a 3 mitosis atípicas por campo de alto poder; centro necrótico y células "fantasma". Dentro del diagnóstico diferencial debe considerarse el pilomatrixoma proliferante, el quiste triquilemal proliferante maligno y el carcinoma de células basales con diferenciación matricial. Los estudios complementarios de inmunohistoquímica no fueron contributorios. (AU)

Pilomatrix carcinoma is the malignant counterpart of pilomatrixoma, which is a benign neoplasm affecting children and adults. It is a rare condition, presenting as a solitary nodule on the head or neck mostly seen in middle age males. It is considered a low grade malignant condition; surgical removal is the treatment of choice. We report the case of a 32-year-old male patient who presented with a nodular lesion of 1.8 cm located on the temporo-occipital region. The section of this nodule showed an encapsulated solid yellow tissue that showed under the microscopy well demarcated borders with basal cells presenting with pleomorphic, hyperchromatic nucleus, prominent nucleolus and 0-3 atypical mitosis per high power field, necrotic center and "ghost cells". The differential diagnosis should include pilomatrixoma proliferans, malignant proliferative trichilemmal cyst and basal-cell carcinoma with matricial differentiation. Complementary immunohistochemistry studies were non-contributory. (AU)

Infarto esplénico embólico / Splenic infarction due to thromboembolism

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