Osteoglycin (Ogn), a class III SLRP member with multiple glycosylation sites, has been proposed to be engaged in cardiac dysfunction and adverse remodeling in human heart failure following myocardial infarction. However, the underlying mechanism remains to be elucidated. Thus, we sought to define the role of Ogn in regulation of the Wnt pathway on myocardial fibrosis and epithelial/endothelial-mesenchymal transformation (EMT/EndMT) in mice with myocarditis. The pathological changes are observed, while hematoxylin-eosin staining and picric acid Sirius red staining were conducted in successfully constructed myocarditis mouse models. Immunohistochemistry and enzymelinked immunosorbent assay were adopted to determine Ogn and β-catenin levels and serum procollagen propeptide concentrations in the mouse myocardial tissues, respectively. Expression of Ogn and Wnt signaling pathway-related factors were measured by reverse transcription quantitative polymerase chain reaction and western blot assay, cell viability by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell cycle distribution and apoptosis by flow cytometry. We saw indicative pathological changes accompanied by many Ogn and β-catenin positive cells and increased serum procollagen propeptide, in the mouse myocardial tissues. Loss function assays showed reduced levels of Ogn, β-catenin, LRP6, TGF-β1, Twist, FSP-1, α-SMA and higher levels of E-cadherin and VE-cadherin, together with decreased proliferation rate, as well as increased apoptosis rate, indicating that the Wnt signaling pathway, proliferation were inhibited while apoptosis was enhanced with upon gene silencing. Coherently, depletion of Ogn inhibits myocardial fibroblasts

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Cardiovascular risk factors have attracted increasing attention in recent years with the acceleration of population aging, amongst which cardiac hypertrophy is the initiating link to heart failure. Pirfenidone is a promising agent for the treatment of idiopathic pulmonary fibrosis and has recently proven to exert inhibitory effects on the inflammatory response. This study proposes to explore the potential pharmacological action of pirfenidone in treating cardiac hypertrophy in a rodent model. Four groups of mice were used in the present study: the control, ISO (5 mg/kg/day) for 7 days, pirfenidone (200 mg/kg/day) for 14 days, and spironolactone (SPI) (200 mg/kg/day) for 14 days groups. Increased heart weight index, left ventricle (LV) weight index, LV wall thickness, declined LV volume, and elevated serum levels of CK-MB, AST, and LDH were observed in ISO-challenged mice, all of which were dramatically reversed by the administration of pirfenidone or SPI. Furthermore, an elevated cross-sectional area of cardiomyocytes in the wheat germ agglutinin (WGA) staining of heart cross-sections, upregulated atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), β-Myosin Heavy Chain (β-MHC), and excessively released tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in cardiac tissues were observed in the ISO group but greatly alleviated by pirfenidone or SPI. Lastly, the promoted expression levels of p-JAK-2/JAK-2 and p-STAT3/STAT-3 in the cardiac tissues of ISO-challenged mice were significantly repressed by pirfenidone or SPI. Collectively, our data reveals a therapeutic property of pirfenidone on ISO-induced cardiac hypertrophy in mice.