Study on congenital renal dysplasia and its molecular biology
Renal hypoplasia is the clinical consequence of renal abnormality, and its typical histopathological feature is metaplasia.
Primary glomeruli and renal tubules, chondroid metaplasia, etc. In recent years, through the application of molecular technology such as target gene and in-situ cloning.
The molecular regulation mechanism of renal development in normal mammals was studied. The pathogenesis of congenital renal dysplasia is as follows
Learn more. In this paper, the molecular biology research of congenital renal dysplasia in recent years will be discussed, and its development prospect will be prospected
Relationship between several gene mutations, transcription regulation disorders and expression changes including growth factors and renal dysplasia
Discuss it.
Renal dysplasia is a congenital disease caused by the abnormal growth and development of the kidney, which has been caused in the past.
Little is known about its mechanism. With the development and application of molecular biotechnology, the occurrence of kidney is expounded from the molecular mechanism.
We have a deeper understanding of the occurrence of renal dysplasia from the molecular biology level. This paper expounds the recent problems.
The research progress of this paper is introduced.
1 nephrogenesis and renal dysplasia
The kidney of normal mammals is located in mesoderm, which differentiates to form the anterior renal duct.
It leads to the formation of mesonephric duct to ureter bud, and renin on both sides of embryo end is induced to differentiate into post-renin.
Kidney embryo base, the embryonic development of kidney is completed by ureter bud and posterior kidney embryo base, the former develops step by step.
It enters the renal pelvis, calyx and collecting duct, and the latter develops into renal tubules and glomeruli, and finally the renal tubules are connected with collecting duct.
Constitute a normal nephron. If the ureter bud and the posterior renal embryo base can not develop and arrange according to the normal degree
Then it will cause renal dysplasia. Renal dysplasia can be partial or complete. Most types
Renal dysplasia with cyst accounts for%, suggesting that all forms of dysplasia have the same formation mechanism.
Clinical common congenital renal dysplasia includes polycystic kidney disease, obstructive renal dysplasia and their relationship with genes.
Related renal dysplasia. An important feature of histopathology is the appearance of primitive renal tubules and metaplastic cartilage. Integrity table
Lateral renal dysplasia can be asymptomatic. In most cases of dysplasia, renal defects are bilateral, which shows that
Gene mutation plays an important role in normal kidney development. Unilateral diseases may be caused by acquired injuries,
This damage destroys the normal expression of genes, and then affects the production of protein, and protein is very important for kidney maturation.
Two Common Renal Dysplasia
2. 1 congenital polycystic kidney dysplasia
Multiple cystic renal dysplasia is a common integrity.
Renal dysplasia is mostly unilateral (14-20% is bilateral), and the affected kidney loses its normal shape and is irregular.
Cysts, renal insufficiency and ureteral obstruction are the most common abdominal masses in newborns.
One of the reasons.
Polycystic dysplasia has a kidney-shaped structure outside the kidney, and most cases are accompanied by ureteral closure. be pregnant
Early polycystic kidney contains essential components for normal development, including uninduced posterior renal embryonic island and branched urine infusion.
At this stage, cystic changes can be identified in all segments of nephron [1]. Postnatal polycystic kidney disease
Histopathological changes include cystic degeneration, enlargement and structural destruction of primitive renal tubules, as well as obvious peritubular characteristics.
The matrix of reaction, the formation of fibromuscular ring, tissue transformation marked by cartilage components, etc.
2.2 Congenital obstructive renal dysplasia
Congenital urinary tract obstruction often occurs at the junction of ureter and bladder in anatomical position.
Urethral valve is an important cause of urinary system obstruction in infants. Histological characteristics of congenital obstructive kidney and polycystic kidney disease.
Renal dysplasia is similar, including cystic changes in nephron segments such as glomerulus, interstitial swelling and structural damage, and bone marrow
There are obvious parenchymal and small straight vascular hypoplasia, fibrous muscle ring around the catheter, various forms of glomeruli and developing kidneys.
Unit paragraph. Like polycystic kidney dysplasia, congenital obstructive kidney shows a series of diseases, the degree of which is related to
The occurrence time of urine flow obstruction in embryo is related [2].
Renal dysplasia syndrome
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Chromosome genetic form of syndrome
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Autosomal dominant inheritance of pointed syndactyly
Asphyxia caused by autosomal recessive thoracic dystrophy
Autosomal recessive inheritance, such as obesity and reproductive dysfunction.
Gill-ear-kidney autosomal dominance
Autosomal recessive inheritance of Campomelic dysplasia
Brain-liver-kidney autosomal recessive inheritance
Fringe autosomal recessive inheritance
Goemine is x-connected
Goldston (hereditary telangiectasia) autosomal recessive?
From Hall pars's
Autosomal recessive inheritance of Ifemark
Recessive inheritance of Madden-Walker autosome
Recessive inheritance of Mei-Gru autosome
Miranda autosomal recessive inheritance
Autosomal recessive inheritance of Senlor-Loken?
Trisomy 16- 18 (Edwards)
Trisomy 13- 15 (Pato)
Trisomy 2 1 (downward)
Autosomal dominance of tuberous sclerosis
Von hippel-Lindau autosomal dominance
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2.3 Renal hypoplasia syndrome
Renal dysplasia syndrome is a hereditary syndrome, including renal malformation, such as cystic dysplasia (see table
)。 Now, some syndrome-specific genes and protein's defects have been clarified. The penetrance of dysplasia phenotype is
Now, a band shows that there are other genes that affect the final phenotype of the kidney. Dysplasia usually involves multiple organs,
It shows that defective genes are related to the basis of normal organogenesis. Pathohistology found that mild cases of this syndrome may be.
Large cysts (such as tuberous sclerosis) appear, and in severe cases, cystic dysplasia and renal failure may occur (Meckel-
Gruber syndrome)
Molecular Biology of Renal Dysplasia
At present, many genes are found to be related to renal dysplasia, such as WT- 1, Pax-2, GDNF and B.
F-2, BMP-7, PDGF, Wnt-4 and other genes were expressed in the embryonic base of the posterior kidney. Pax-2、c-ret、BMP-7、α3β
1 was expressed in ureteral bud. When these genes are lacking or destroyed, the kidney cannot develop normally [3]
]。 Sonnenberg et al. [4] studied specific antibodies and radiolabeled complement RNA and DNA probes to determine
Polypeptide growth factor, heparin structural growth factor and its receptor, extracellular matrix molecules and cell surface modification were introduced.
Specific expression positions of synaptophysin and other genes in renal development. For example, hepatocyte growth factor is mainly in the post-nephroblastoma gene.
Expression, and its receptor c-met is expressed in ureteral reproductive epithelium. There are two types of this polypeptide and its receptor.
Intracellular expression showed that ureteral catheter could induce the formation of posterior renal interstitium. Schuchardt et al [5] passed.
Through gene recombination and preparation of homozygous zero mutant mice, some genes and polypeptides affecting kidney development were found, such as
Transfer growth factor-β, hepatocyte growth factor, insulin-like growth factor-Ⅱ, according to the final table.
Type A infers the role of specific genes in normal nephrogenesis. Tyrosine kinase receptor c-ret in branched ureteral catheter
Tube and ligand-glial-derived neurotrophic factor. When the mouse c-ret gene is destroyed, it is composed of
Resulting in hypoplasia of the whole kidney. Protein encoded by transcription factor gene can bind to DNA and has the function of regulating other gene tables.
The function of. During the development of mammalian kidney, Wilms' tumor genes WT- 1 and Pax2 both encode transcription factors.
Its expression forms affect the differentiation of renal cells [6, 7]. Genetic syndrome is related to abnormal kidney formation, as listed in the table.
Some diseases and syndromes are inherited, and some specific gene defects have been located by in-situ cloning technology [
8]。 These syndromes may have significant phenotypic variation in family members. This situation is not true in homozygotes.
Mutant mice see similar variation, that is, the final phenotype of kidney depends on the genetic background of experimental mice.
The occurrence of renal dysplasia is caused by several different genetic defects or teratogenic factors encountered during embryonic development.
The final result of various genetic regulatory obstacles. Renal Interstitial-Epithelial Transformation and the Bifurcation and Growth of Ureter
, is guided by a complex and huge gene system, some genes are kidney-specific and some are non-specific.
Yes Some growth factor genes, although they are active in nephrogenesis, will not produce shadows when they are destroyed.
It affects the normal development of the kidney, which means that the genes normally expressed in the developing kidney overlap in function [9]. another
One possibility is that the destruction of this normal expression plays a role in the occurrence and development of renal dysplasia, or
Is the cause of renal dysplasia.
Renal interstitial defects can lead to renal dysplasia. In addition, gene imbalance and dislocation expression may be harmful to the kidney.
Stunted growth played a role. Clinically, there are isolated polycystic kidney dysplasia and obstructive renal dysplasia.
Parallel cases. Both congenital and experimental single gene mutations can lead to cystic renal dysplasia. These genes
Mutations can change interconnections. Theoretically, mutation can affect: ① embryoid proliferation and differentiation of ureteral catheter.
Expression of peptides and matrix proteins needed for branching; (2) The responsiveness of ureteral catheter to fetal basal signals of posterior kidney; ③ Lose
The expression of urinary catheter can initiate and maintain the protein needed to induce the basal epithelium of renal embryos; ④ Fetal base of posterior kidney is sensitive to these letters.
Reaction ability; ⑤ The ability of the basal cells of ureter bud and posterior kidney embryo to respond to signals [10].
Recently, phosphoinositide glycoprotein gene, abbreviated as GPC3 gene, has been isolated. GPC3 deletion and abundance
Cystic renal dysplasia [1 1]. Although single gene and polygene defects will eventually lead to renal dysplasia, but
Its phenotype may be determined by initial gene regulation disorder or expression change, such as congenital obstructive and cystic.
Renal dysplasia [12, 13]. Polycystic dysplasia kidney with growth factor gene in cystic epithelium and stroma.
Change. Over-expression of angiotensin and transfer growth factor in obstructive developing kidney of mice [14]. study
It has been proved that Pax2 and Bcl-2 are the same factors that promote tubular epithelial degeneration in the region of abnormal renal development.
Overexpression [15, 16]. This study may provide important clues for the pathogenesis of various forms of renal dysplasia.
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