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Wnt signaling in spermatogenesis and male infertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Vertika Singh, Meghali Joshi, Kiran Singh, Rajender Singh
Sox9 can trigger the expression of its downstream targets, FGF9 and PGDS (prostaglandin D synthase) (40). Both FGF9 and PGDS promote the proliferation and differentiation of the Sertoli cells, thus promoting the masculinization of the testis (40). A shift of balance from Sox9/FGF9 to Wnt/β-catenin signaling can result in a transition from male to female in various species (44,45). In-frame missense and splicing mutations in the MAP kinase pathway gene MAP3K1 tilt the balance from the male to the female sex-determining pathway, resulting in the 46,XY disorder of sex development. These MAP3K1 mutations arbitrate this balance by enhancing the β-catenin activity and WNT/β-catenin/FOXL2 expression and by reducing the expression of SOX9/FGF9/FGFR2/SRY (46). In summary, Wnt signaling plays a major inhibitory role in testis determination.
Articular Cartilage Development
Published in Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi, Articular Cartilage, 2017
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi
Other relevant transcription factors during cartilage development include Pax1 and scleraxis (Table 2.2), which activate cartilage-specific genes (Cserjesi et al. 1995; Sosic et al. 1997). Members of the Sox protein family, specifically Sox9, Sox5, and Sox6, are also expressed in prechondrogenic cells, with Sox9 being necessary for the mesenchymal aggregation (Bi et al. 1999). This differentiation of mesenchymal cells into chondroblasts and further into chondrocytes is under the control of BMP2, BMP4 and 7, and TGF-β (Cole et al. 2003; Tickle 2003). A temporal expression profile of various transcription factors is depicted in Figure 2.11.
Chondrosarcoma
Published in Dongyou Liu, Tumors and Cancers, 2017
Dedifferentiated chondrosarcoma is a grade 4 tumor characterized by a bimorphic histology with a well-differentiated cartilaginous component and a dedifferentiated, noncartilaginous component. The tumor stains positive for SOX9 and has IDH1 and IDH2 overexpression.
IL-6, IL-1β and TNF-α regulation of the chondrocyte phenotype: a possible mechanism of haemophilic cartilage destruction
Published in Hematology, 2023
Liujie Zheng, Zhiwei Han, Dasheng Luo, Jiale Li, Nanyu Pang, Mingyang Ding, Houlong Ye, Keyan Zhu, Yunfeng Yao
FGF23 is a protein that is a member of FGF19 subfamily which has been widely studied in phosphate and vitamin D metabolism over the last few decades [4–6]. This secretory protein has also been confirmed to play a crucial part in regulating cartilage metabolism. Excess FGF23 has a strong inhibitory effect on chondrocyte proliferation. FGF23 overload has been shown to upregulate MMP13 expression in chondrocytes resulting in cartilage ECM degradation and subsequent cartilage destruction [7,8]. SOX9, a member of the SOX (SRY-related HMG-box) family that is mainly secreted by chondrocytes, could also be a vital regulator of the cartilage metabolic cycle [9,10]. Low levels of SOX9 in cartilage may inhibit chondrogenesis, cartilage regeneration and differentiation [11]. Additionally, down-regulated expression of SOX9 may upregulate the MMP13 expression in chondrocytes [8]. In a previous study, we found higher levels of FGF23 and lower levels of SOX9 in HA cartilage compared with osteoarthritis (OA), and showed that the expression of FGF23 and SOX9 affected iron regulation in chondrocytes [12]. Like iron, proinflammatory cytokines also have a key role in HA cartilage degradation pathogenesis, but their relationship to phenotype alterations in chondrocytes remains unclear.
The use of in silico extreme pathway (ExPa) analysis to identify conserved reproductive transcriptional-regulatory networks in humans, mice, and zebrafish
Published in Systems Biology in Reproductive Medicine, 2023
Almost all male genes from SRY to AR, to lesser or greater extents, coregulated with one another. FGF9, PGD2, DHH, DKK1, and AR appear near constitutively coactive with ExPa predicted levels of ≥33% with all male genes (Figure 3A). FGF9 and PGD2 are essential for maintaining elevated SOX9 activity in somatic cells and for perpetuating the male developmental morphogenetic program. As a decisive gene and TF, SOX9 locks-in its own irrevocable expression in partnership with FGF9 and PGD2 (Warr and Greenfield 2012; Capel 2017). The three factors, i.e., SOX9, FGF9, and PGD2 do not directly interact with one another. Instead, SOX9 acts as a TF up-regulating FGF9 production, which blocks the activation of WNT4, a TF responsible for sex differentiation to the female phenotype (Eggers and Sinclair 2012). Whereas PGD2 regulates SOX9 nuclear translocation and downstream activations of TFs involved in sex determination and differentiation (Chen et al. 2017). The signaling molecules DHH and DKK1 are essential for mediating the differentiation of male gonad somatic cells and act as inhibitors of the female WNT signaling pathway (Glinka et al. 1998; Eggers and Sinclair 2012). Finally, the constitutive AR expression supports its role as a receptor that is responsive to androgen productions from somatic cells, and for instantiating virilization during fetal, pubertal, and adult life stages of the male sexual phenotype (Rey 2020) (Figure 3A).
Novel therapeutic perspectives for crescentic glomerulonephritis through targeting parietal epithelial cell activation and proliferation
Published in Expert Opinion on Therapeutic Targets, 2023
Yanjie Huang, Xueru Zhao, Qiushuang Zhang, Xiaoqing Yang, Gailing Hou, Chaoqun Peng, Mengzhen Jia, Li Zhou, Tatsuo Yamamoto, Jian Zheng
Under physiological conditions, PECs can be divided into three subgroups with different molecular phenotypes. PECs localized to the urinary pole expressed stem cell markers, CD133 and CD24, but did not express podocytes markers, such as nestin and podocalyxin (PDX), and this subpopulation of PECs (CD133+ CD24+ PDX-) could regenerate both tubular cells and podocytes. In contrast, PECs between the urinary and vascular poles expressed stem cell and podocyte markers, and this subpopulation (CD133+ CD24+ PDX+) could regenerate only podocytes. PECs localized to the vascular pole did not exhibit CD133 or CD24 expression but displayed phenotypic features of differentiated podocytes. PECs (CD133-CD24-PDX+) have most of the characteristics of mature podocytes and cannot proliferate or differentiate [84]. Therefore, PECs have the characteristics of renal progenitor cells and may serve as progenitor cells for podocytes. Prochnicki et al. analyzed the cell fate of sex-determining region Y-box 9 (SOX9)+ PECs in anti-GBM mice and showed that SOX9 recently emerged as another marker of PECs with progenitor properties in 2018 [85]. SOX9 is a member of the Sry-related high-mobility group box of transcription factors that is known as a marker for stem cell or progenitor populations in several adult organs and developmental processes. SOX9 is expressed in a subpopulation of PECs [86,87]. These studies showed that transdifferentiating cells into podocytes during the disease time-course could be PECs with stem cell properties (SOX9+).