Related Experiment Video
Updated: May 9, 2026
07:15
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
SIRPα signaling regulates podocyte structure and function.
Satoshi Takahashi1, Mai Tomioka, Keiju Hiromura
1Dept. of Medicine and Clinical Science, Gunma Univ. Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan. hiromura@gunma-u.ac.jp.
American Journal of Physiology. Renal Physiology
|July 12, 2013
Summary
Signal-regulatory protein-α (SIRPα) plays a crucial role in maintaining podocyte structure and kidney function. Loss of SIRPα in podocytes leads to abnormal kidney filtration and increased susceptibility to nephropathy.
Area of Science:
- Nephrology
- Cell Biology
- Immunology
Background:
- Signal-regulatory protein-α (SIRPα) is a transmembrane protein involved in intracellular signaling via tyrosine phosphorylation.
- SIRPα is expressed in podocytes and is a major tyrosine-phosphorylated protein in the glomeruli.
Purpose of the Study:
- To investigate the role of SIRPα in podocyte structure and function.
- To assess the impact of SIRPα deficiency in podocytes on kidney physiology and response to nephrotoxic agents.
Main Methods:
- Generation and analysis of knockin mice lacking the cytoplasmic region of SIRPα (SIRPα-mutant mice).
- Light and electron microscopy of kidney morphology.
- Assessment of renal function and albuminuria.
- Adriamycin-induced nephropathy model.
Main Results:
- SIRPα-mutant mice exhibited abnormal podocyte foot processes and impaired renal function with mild albuminuria.
- SIRPα-mutant mice developed severe albuminuria and focal glomerulosclerosis after adriamycin injection.
- Wild-type mice were resistant to adriamycin-induced nephropathy.
Conclusions:
- SIRPα is essential for maintaining podocyte structure and function as a filtration barrier.
- SIRPα plays a critical role in protecting the kidneys under both physiological and pathological conditions.
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
01:22PI3K/mTOR/AKT Signaling Pathway
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 rapamycin-insensitive companion...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
01:11IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...