The Role of Bone Morphogenetic Protein 4 in Ovarian Function and Diseases

Yang, Dongyong; Yang, Xiao; Dai, Fangfang; Wang, Yanqing; Yang, Yi; Hu, Min; Cheng, Yanxiang

doi:10.1007/s43032-021-00600-8

Cited by 9 publications

(5 citation statements)

References 165 publications

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“…The expression levels of BMP4 have been extensively studied in various cancer cell lines and tumor tissues of human and animal origin, by a variety of methods. This protein was detected in both normal and tumor tissues at variable levels ( Rothhammer et al, 2005 ; Deng et al, 2007 ; Goulley et al, 2007 ; Yang et al, 2021 ). Comparative immunohistochemical analysis of BMP4 expression in different tumors and corresponding normal tissues ( Alarmo et al, 2013 ) has revealed a strong granular BMP4 staining pattern in several normal human tissues (e.g., stomach, esophagus, liver, and spleen), indicating a significant function of BMP4 in tissue homeostasis.…”

Section: Bone Morphogenetic Protein 4/bmpr Signaling In Cancermentioning

confidence: 99%

Targeting Stress Erythropoiesis Pathways in Cancer

et al. 2022

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Cancer-related anemia (CRA) is a common multifactorial disorder that adversely affects the quality of life and overall prognosis in patients with cancer. Safety concerns associated with the most common CRA treatment options, including intravenous iron therapy and erythropoietic-stimulating agents, have often resulted in no or suboptimal anemia management for many cancer patients. Chronic anemia creates a vital need to restore normal erythropoietic output and therefore activates the mechanisms of stress erythropoiesis (SE). A growing body of evidence demonstrates that bone morphogenetic protein 4 (BMP4) signaling, along with glucocorticoids, erythropoietin, stem cell factor, growth differentiation factor 15 (GDF15) and hypoxia-inducible factors, plays a pivotal role in SE. Nevertheless, a chronic state of SE may lead to ineffective erythropoiesis, characterized by the expansion of erythroid progenitor pool, that largely fails to differentiate and give rise to mature red blood cells, further aggravating CRA. In this review, we summarize the current state of knowledge on the emerging roles for stress erythroid progenitors and activated SE pathways in tumor progression, highlighting the urgent need to suppress ineffective erythropoiesis in cancer patients and develop an optimal treatment strategy as well as a personalized approach to CRA management.

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Section: Bone Morphogenetic Protein 4/bmpr Signaling In Cancermentioning

confidence: 99%

Targeting Stress Erythropoiesis Pathways in Cancer

et al. 2022

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“…The overexpression of the BMPR1A and BMPR1B genes in ovarian granulosa cells inhibits the occurrence of mouse granulose tumors, while the knockout of BMPR1A revealed less spontaneous ovulation and reduced fertility in mice [36]. Studies have shown that BMPR1B regulates the differentiation of granulosa cells and follicle development by participating in the signal transduction of BMP2, BMP4, BMP6, BMP7, BMP15, and GDF5, thus affecting the reproductive cycle of mammals [37,38]. In particular, CYP19A1 can convert androgens into estrogen, and estrogen can inhibit apoptosis in granulosa cells and promote its differentiation by increasing the expression of LHCGR, the LH receptor, thus regulating follicle development [39,40].…”

Section: Discussionmentioning

confidence: 99%

Behavioral and Physiological Differences in Female Rabbits at Different Stages of the Estrous Cycle

Chen,

Jin,

Yang

et al. 2023

Animals

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Estrus involves a series of complex physiological signs and changes in behavior before ovulation, which play a crucial role in animal reproduction. However, there have been few studies that evaluate behaviors during the different stages of estrus cycle in female rabbits. Therefore, more detailed information is needed on distinguishing the various stages of the estrous cycle. This study explored the behavioral and physiological differences at various estrous cycle stages in female New Zealand White rabbits. The continuous recording method was employed to record the daily behaviors of twenty postpartum female rabbits during the estrous cycle. Compared with the diestrus stage, the duration of foraging and drinking behavior in estrus decreased significantly, and the frequency of grooming and biting behaviors increased (p < 0.05). Differences in reproductive hormone levels (FSH, LH, P4, and E2) and follicle development were measured at each stage via ELISA and HE staining. The FSH and LH levels showed an increasing trend and then decreased, with the lowest being in late estrus (p < 0.05). The P4 level was the lowest in estrus (p < 0.05), and E2 showed a gradually increasing trend. There was no significant difference in the number of primordial follicles at each stage, but the number of primary follicles in estrus was significantly higher than at the other stages (p < 0.05). To further understand the molecular regulation mechanism of the estrous cycle in female rabbits, we analyzed the ovarian transcription patterns of female rabbits in diestrus (D group) and estrus (E group) employing RNA-seq. A total of 967 differentially expressed genes (DEGs) were screened from the ovaries of female rabbits between the diestrus and estrus groups. A KEGG analysis of DEGs enriched in the estrogen signaling pathway, aldosterone synthesis, and secretion pathway, such as CYP19A1 and IGF1R, was performed. The rabbits’ behavior, related physiological hormones, and molecular regulation also differed at different estrous cycle stages. The results provide recommendations for the adequate management practices of postpartum re-estrus and breeding female rabbits.

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“…Since the successful cloning and identification of the first BMP genes in the 1980s [ 2 ], more than 40 BMP genes have been identified. BMPs are crucial for osteoblast differentiation and bone formation and have been implicated in cancer development by promoting the growth and invasion of cancer cells [ 3 , 4 ]. These genes also regulate various physiological systems, including the circulatory, gastrointestinal, pulmonary, urinary, reproductive, and neurological systems [ 5 ], playing critical roles in embryonic development, growth, and differentiation [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Genome-wide identification and structural analysis of the BMP gene family in Triplophysa dalaica

Zhang,

Yu,

Han

et al. 2024

BMC Genomics

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Background Bone morphogenetic proteins (BMPs) are part of the transforming growth factor beta (TGF-β) superfamily and play crucial roles in bone development, as well as in the formation and maintenance of various organs. Triplophysa dalaica, a small loach fish that primarily inhabits relatively high elevations and cooler water bodies, was the focus of this study. Understanding the function of BMP genes during the morphogenesis of T. dalaica helps to clarify the mechanisms of its evolution and serves as a reference for the study of BMP genes in other bony fishes. The data for the T. dalaica transcriptome and genome used in this investigation were derived from the outcomes of our laboratory sequencing. Results This study identified a total of 26 BMP genes, all of which, except for BMP1, possess similar TGF-β structural domains. We conducted an analysis of these 26 BMP genes, examining their physicochemical properties, subcellular localization, phylogenetic relationships, covariance within and among species, chromosomal localization, gene structure, conserved motifs, conserved structural domains, and expression patterns. Our findings indicated that three BMP genes were associated with unstable proteins, while 11 BMP genes were located within the extracellular matrix. Furthermore, some BMP genes were duplicated, with the majority being enriched in the GO:0008083 pathway, which is related to growth factor activity. It was hypothesized that genes within the BMP1/3/11/15 subgroup (Group I) play a significant role in the growth and development of T. dalaica. By analyzing the expression patterns of proteins in nine tissues (gonad, kidney, gill, spleen, brain, liver, fin, heart, and muscle), we found that BMP genes play diverse regulatory roles during different stages of growth and development and exhibit characteristics of division of labor. Conclusions This study contributes to a deeper understanding of BMP gene family member expression patterns in high-altitude, high-salinity environments and provides valuable insights for future research on the BMP gene family in bony fishes.

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The Role of Bone Morphogenetic Protein 4 in Ovarian Function and Diseases

Cited by 9 publications

References 165 publications

Targeting Stress Erythropoiesis Pathways in Cancer

Targeting Stress Erythropoiesis Pathways in Cancer

Behavioral and Physiological Differences in Female Rabbits at Different Stages of the Estrous Cycle

Genome-wide identification and structural analysis of the BMP gene family in Triplophysa dalaica

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