Leptin, secreted by the adipose tissue and known to be related to obesity, is considered to be involved in the onset and progression of colorectal cancer. However, the exact role of leptin in colorectal carcinogenesis is still unclear, as several controversial reports have been published on the various systemic effects of leptin. The aim of this study was to clarify the local and precise roles of leptin receptor (LEPR)-mediated signaling in colonic carcinogenesis using intestinal epithelium-specific LEPRb conditional knockout (cKO) mice. We produced and used colonic epithelium-specific LEPRb cKO mice to investigate the carcinogen-induced formation of aberrant crypt foci (ACF) and tumors in the colon, using their littermates as control. There were no differences in the body weight or systemic condition between the control and cKO mice. The tumor sizes and number of large-sized tumors were significantly lower in the cKO mice as compared with those in the control mice. On the other hand, there was no significant difference in the proliferative activity of the normal colonic epithelial cells or ACF formation between the control and cKO mice. In the control mice, marked increase of the LEPRb expression level was observed in the colonic tumors as compared with that in the normal epithelium; furthermore, signal transducer and activator of transcription (STAT3) was activated in the tumor cells. These findings suggest that STAT3 is one of the important molecules downstream of LEPRb, and LEPRb/STAT3 signaling controls tumor cell proliferation. We demonstrated the importance of local/regional LEPR-mediated signaling in colorectal carcinogenesis.
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http://dx.doi.org/10.1093/carcin/bgu135 | DOI Listing |
Development
January 2025
School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia.
A successful mitosis-to-meiosis transition in germ cells is essential for fertility in sexually reproducing organisms. In mice and humans, it is established that expression of STRA8 is critical for meiotic onset in both sexes. Here we show that BMP signalling is also essential, not for STRA8 induction but for correct meiotic progression in female mouse fetal germ cells.
View Article and Find Full Text PDFCell Metab
January 2025
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China; National Key Laboratory of Immunity and Inflammation, Institute of Immunology, Navy Medical University, Shanghai 200433, China; Institute of Immunology, College of Life Sciences, Nankai University, Tianjin 300071, China; Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China. Electronic address:
Bacterial infection reprograms cellular metabolism and epigenetic status, but how the metabolic-epigenetic crosstalk empowers host antibacterial defense remains unclear. Here, we report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a sensor for metabolite adenine to launch an antimicrobial innate response through increasing Il1b transcription. Myeloid cell-specific Hnrnpa2b1-cKO mice are more susceptible to bacterial infection, while interleukin 1 beta (IL-1β) supplementation rescues the phenotype.
View Article and Find Full Text PDFOsteoarthr Cartil Open
March 2025
Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
Objective: Osteoarthritis is a chronic, debilitating disease that causes long-term pain and immobility. Germline deletion of Phlpp1 or administration of small molecules that inhibit Phlpp1 prevents post-traumatic osteoarthritis (PTOA) in mice. However, the chondrocyte-intrinsic role of Phlpp1 in PTOA progression is unknown.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
The dysfunction of stress granules (SGs) plays a crucial role in the pathogenesis of various neurological disorders, with T cell intracellular antigen 1 (TIA1) being a key component of SGs. However, the role and mechanism of TIA1-mediated SGs in experimental autoimmune encephalomyelitis (EAE) remain unclear. In this study, upregulation of TIA1, its translocation from the nucleus to the cytoplasm, and co-localization with G3BP1 (a marker of SGs) are observed in the spinal cord neurons of EAE mice.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Impaired autophagy is reported to promote osteoarthritis (OA). However, the mechanism by which autophagy in regulating meniscus degeneration and OA remains unclear. Here, unconvered aberrant energetic metabolism pattern in meniscus cells with OA is uncovered first, which results in lower adenosine triphosphate (ATP) production.
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