Related Experiment Video
Updated: May 21, 2025
09:43
Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
2.8K
Ras-MAPK pathway in patients with lupus nephritis
Changming Zhang1,2, Xiaoman Jing2, Yangyang Zhang1
1National Clinical Research Center of Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Lupus Science & Medicine
|March 18, 2025
Summary
RASopathy mutations can cause lupus nephritis, a condition primarily affecting the kidneys. Genetic screening for RASopathy is recommended for early-onset lupus patients.
Area of Science:
- Genetics
- Immunology
- Nephrology
Background:
- RASopathy is caused by pathogenic mutations in genes of the Ras/mitogen-activated protein kinase (Ras-MAPK) pathway.
- This study investigates five unrelated patients with Systemic Lupus Erythematosus (SLE) carrying RASopathy-associated mutations.
Purpose of the Study:
- To identify and characterize RASopathy-associated mutations in patients with SLE.
- To investigate the activity of the Ras-MAPK pathway in these patients.
Main Methods:
- Whole-exome/whole-genome sequencing was used to identify pathogenic variants.
- Ras-MAPK pathway activity was assessed in peripheral blood mononuclear cells (PBMC) via RNA sequencing and in kidneys using the NephroSeq database.
Main Results:
- Five pathogenic variants in four Ras-MAPK genes (NRAS, ARAF, KRAS, PTPN11) were identified.
- Kidney injury, including nephrotic syndrome and lupus nephritis, was the primary clinical manifestation.
- The Ras-MAPK pathway was found to be activated in both PBMC and kidney tissues of patients with lupus nephritis.
Conclusions:
- Kidney involvement is a significant feature of RASopathy's clinical spectrum.
- Genetic screening for RASopathy should be considered in patients presenting with early-onset lupus.
More Related Videos
Related Concept Videos
01:07MAPK Signaling Cascades
5.0K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.0K
01:20The JAK-STAT Signaling Pathway
8.6K
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...
8.6K
01:22PI3K/mTOR/AKT Signaling Pathway
3.3K
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...
3.3K
02:26NF-κB-dependent Signaling Pathway
7.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.2K
03:03mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
01:20Renal Corpuscle
1.4K
The glomerulus and Bowman's capsule are two essential components of the nephron, which is the functional unit of the kidney. These microscopic structures play a critical role in the process of blood filtration to produce urine.
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
1.4K