Interleukin-driven insulin-like growth factor promotes prostatic inflammatory hyperplasia.
Alana M Hahn1, Jason D Myers1, Eliza K McFarland1
1Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana (A.M.H., J.D.M., T.J.J.); Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, Wisconsin (E.K.M., S.L.); and Melvin and Bren Simon Cancer Center, Indiana Basic Urological Research Working Group, Indiana University, Indianapolis, Indiana (T.J.J.).
The Journal of Pharmacology and Experimental Therapeutics
|October 9, 2014
Summary
Inflammation induces insulin-like growth factors (IGFs) in the prostate, driving cell proliferation. This discovery offers new therapeutic targets for benign prostatic hyperplasia and prostate cancer by modulating IGF signaling.
Area of Science:
- Urology
- Inflammation research
- Endocrinology
Background:
- Prostatic inflammation is linked to benign prostatic hyperplasia and prostate cancer.
- Mechanisms connecting inflammation to prostate cell proliferation are not fully understood.
Purpose of the Study:
- To investigate the role of insulin-like growth factors (IGFs) in inflammation-induced prostatic hyperplasia.
- To elucidate the signaling pathways involved in prostatic growth during inflammation.
Main Methods:
- Utilized genetic models and in vivo IGF receptor blockade.
- Analyzed human prostatic hyperplasia tissues for IGF pathway activation.
- Investigated the role of interleukin-1 (IL-1) in IGF signaling.
Main Results:
- Inflammation induces IGFs, which are crucial for the proliferative response.
- Hyperplastic growth in response to inflammation is dependent on IL-1-driven IGF signaling.
- Human prostatic hyperplasia shows localized IGF pathway activation at inflammatory foci.
Conclusions:
- Inflammation-induced epithelial proliferation and hyperplasia involve the induction of developmental growth factors like IGFs.
- Establishes a link between inflammatory and developmental signaling in the prostate.
- Provides a mechanistic basis for targeting the IGF pathway in proliferative prostate diseases.
More Related Videos
Related Concept Videos
01:05Insulin Secretory Vesicles
6.2K
Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
6.2K
01:22PI3K/mTOR/AKT Signaling Pathway
5.1K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.1K
01:26Type I Diabetes II: Pathophysiology
23
Type 1 diabetes mellitus arises from an immune-mediated destruction of pancreatic β-cells, resulting in an absolute deficiency of insulin. This process develops in genetically susceptible individuals when autoimmunity, environmental exposures, and immunologic dysregulation converge to trigger a targeted attack on the insulin-producing cells of the pancreas. The β-cells are located within the islets of Langerhans and are essential for regulating blood glucose by facilitating cellular...
23
01:28Insulin: The Receptor and Signaling Pathways
5.9K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
5.9K
01:25Inflammatory Bowel Disease III: Crohn's Disease
19
Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
19
01:26Cellular Adaptation III: Hyperplasia
19
Hyperplasia is an increase in the number of cells in a tissue or organ due to enhanced cell division. It is an adaptive, controlled response to stimuli such as injury, hormones, or stress, involving mitosis to produce genetically identical cells and support tissue repair and regeneration.Tissue CapacityCertain tissues, including the epidermis, intestinal epithelium, bone marrow, and fibroblasts, have a high potential for hyperplasia. Others, such as bone, cartilage, and smooth muscle, show...
19