Identification and functional activity of matrix-remodeling associated 5 (MXRA5) in benign hyperplastic prostate

Xiao, He; Jiang, Ye; He, Weixiang; Xu, Dongmei; Chen, Ping; Liu, Daoquan; Liu, Jianmin; Wang, Xinghuan; DiSanto, Michael E.; Zhang, Xinhua

doi:10.18632/aging.103175

Cited by 27 publications

(21 citation statements)

References 33 publications

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“…Three gene expression profiling datasets (GSE6099 14 , GSE3868 42 , and GSE119195 43 ) were obtained from GEO ( https://www.ncbi.nlm.nih.gov/geo/ ) of the National Center for Biotechnology Information and the mRNA expression profiles of SMO cascades between human BPH specimens and human NP specimens were analyzed. Meanwhile, the Oncomine database ( https://www.oncomine.org/ ) was used for the transcriptional validation of our concerned genes.…”

Section: Methodsmentioning

confidence: 99%

Smoothened inhibition leads to decreased cell proliferation and suppressed tissue fibrosis in the development of benign prostatic hyperplasia

et al. 2021

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Benign prostatic hyperplasia (BPH) is a common disease in aging males. It has been proven that the Hedgehog (HH) is implied as an effective and fundamental regulatory growth factor signal for organogenesis, homeostasis, and regeneration. Smoothened (SMO), as the major control point of HH signals, activates aberrantly in most human solid tumors. However, the specific function of SMO and its downstream glioma-associated oncogene (GLI) family in BPH has not been well understood. Here, we first revealed that the SMO cascade was upregulated in BPH tissues and was localized in both the stromal and the epithelium compartments of human prostate tissues. Cyclopamine, as a specific SMO inhibitor, was incubated with BPH-1 and WPMY-1, and intraperitoneally injected into a BPH rat model established by castration with testosterone supplementation. SMO inhibition could induce cell apoptosis, cell cycle arrest at the G0/G1 phase, and a reduction of tissue fibrosis markers, both in vitro and in vivo. Finally, a tissue microarray, containing 104 BPH specimens, was constructed to analyze the correlations between the expression of SMO cascade and clinical parameters. The GLI2 was correlated positively with nocturia and negatively with fPSA. The GLI3 was in a positive relationship with International Prostate Symptom Score and nocturia. In conclusion, our study suggested that SMO cascade could play important roles in the development of BPH and it might be rediscovered as a promising therapeutic target for BPH.

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Section: Methodsmentioning

confidence: 99%

Smoothened inhibition leads to decreased cell proliferation and suppressed tissue fibrosis in the development of benign prostatic hyperplasia

et al. 2021

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“…MXRA5, a member of the MXRA protein family, plays an important role in cell adhesion and ECM remodeling (32). The protein is found in humans that is encoded by the MXRA5 gene, which contains 7 leucinerich repeats and 13 immunoglobulin-like C2-type domains related to perlecan with a molecular weight of 312KD…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis and Identification of Genes and Pathways in Ischemic Cardiomyopathy

Cao

Liu

et al. 2021

Preprint

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BackgroundIschemic cardiomyopathy (ICM) is considered to be the common cause of heart failure, which has high prevalence and mortality. This study aimed to investigate the different expressed genes (DEGs) and pathways in the pathogenesis of ICM using bioinformatics analysis.MethodsThe control and ICM datasets GSE116250，GSE46224 and GSE5406 were collected from the gene expression omnibus (GEO) database. DEGs were identified using limma package of R software and co-expressed genes were identified with Venn diagrams. Then, the gene otology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explored the biological functions and signaling pathways. Protein-protein interaction (PPI) networks were assembled with Cytoscape software to identify hub genes related to the pathogenesis of ICM.ResultsA total of 844 DEGs were screened from GSE116250, of which 447 up-regulated and 397 down-regulated genes respectively. A total of 99 DEGs were singled out from GSE46224, of which 58 up-regulated and 41 down-regulated genes respectively. 30 DEGs were screened from GSE5406, including 10 genes with up-regulated expression and 20 genes with down-regulated expression. 5 up-regulated and 3 down-regulated co-expressed DEGs were intersected in three datasets. GO and KEGG pathway analyses revealed that DEGs mainly enriched in collagen fibril organization, protein digestion and absorption, AGE-RAGE signaling pathway and other related pathways. Collagen alpha-1(III) chain (COL3A1), collagen alpha-2(I) chain (COL1A2) and lumican (LUM) are the three hub genes in all three datasets through PPI network analysis. The expression of 5 DEGs (SERPINA3, FCN3, COL3A1, HBB, MXRA5) in heart tissues by qRT-PCR results were consistent with our GEO analysis, while expression of 3 DEGs (ASPN, LUM, COL1A2) were opposite with GEO analysis.ConclusionsThese findings from this bioinformatics network analysis investigated key hub genes, which contributed to better understand the mechanism and new therapeutic targets of ICM.

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“…[15][16][17] Indeed, we recently conducted a microarray (SN:GSE119195) analysis and obtained hundreds of differentially expressed genes (DEGs) between hyperplastic and normal prostate, and found that IGF-1 is one of the highly altered DEGs. 18 At present, IGF-1 secretion by M2 macrophages is well documented, 19 which can alter the phagocytic function of nonspecialized phagocytes in a paracrine manner 20 and trigger the proliferation and hypertrophy of adipose tissue via enhancement of angiogenesis. 21 Meanwhile, recent studies have also shown that macrophages, such as M2a macrophages, 13,22 can produce IGF-1 in response to the cytokine IL-4.…”

Section: The Mechanismsmentioning

confidence: 99%

M2a macrophage can rescue proliferation and gene expression of benign prostate hyperplasia epithelial and stroma cells from insulin‐like growth factor 1 knockdown

Qian

Liu

et al. 2021

The Prostate

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Background Benign prostatic hyperplasia (BPH) is a common disease in elderly men and is often accompanied by chronic inflammation. Macrophages (several subtypes) are the main inflammatory cells that infiltrate the hyperplastic prostate and are found to secrete cytokines and growth factors. The current study aims to explore the effect of M2a macrophages on the development of BPH via insulin‐like growth factor 1 (IGF‐1). Methods Human prostate tissues, prostate, and monocyte cell lines (WPMY‐1, BPH‐1, and THP‐1) were used. THP‐1 was polarized into several subtypes with cytokines. The expression and localization of IGF‐1 and M2 macrophages were determined via immunofluorescent staining, quantitative real‐time polymerase chain reaction, and Western blot analysis. Flow cytometry and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assays were used to investigate the effects of different subtypes of macrophages on prostate cells. IGF‐1 in WPMY‐1 and BPH‐1 cells was silenced and cocultured with or without M2a macrophages. Cell proliferation, apoptosis, cell cycle, epithelial–mesenchymal transition (EMT), and fibrosis processes were examined. Results The polarized subtypes of macrophages were verified by amplifying their specific markers. M2a macrophages enhanced prostate cell proliferation more significantly and CD206 was more expressed in hyperplastic prostate. IGF‐1 was localized in both epithelial and stromal components of prostate and upregulated in BPH tissues. M2a macrophages expressed more IGF‐1 than other subtypes. Knockdown of IGF‐1 in WPMY‐1 and BPH‐1 cells attenuated cell proliferation, promoted cell apoptosis, retarded cell cycle at the G0/G1 phase, and suppressed the EMT process in BPH‐1 cells as well as the fibrotic process in WPMY‐1 cells, which was reversible when cocultured with M2a macrophages. Conclusion These data demonstrated that knockdown of IGF‐1 expression in cultured BPH epithelial and stromal cells reduces proliferation and increases apoptosis. These effects are reversed by coculture with M2a macrophages.

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Identification and functional activity of matrix-remodeling associated 5 (MXRA5) in benign hyperplastic prostate

Cited by 27 publications

References 33 publications

Smoothened inhibition leads to decreased cell proliferation and suppressed tissue fibrosis in the development of benign prostatic hyperplasia

Smoothened inhibition leads to decreased cell proliferation and suppressed tissue fibrosis in the development of benign prostatic hyperplasia

Bioinformatics Analysis and Identification of Genes and Pathways in Ischemic Cardiomyopathy

M2a macrophage can rescue proliferation and gene expression of benign prostate hyperplasia epithelial and stroma cells from insulin‐like growth factor 1 knockdown

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