Morphometric study of glomerular basement membrane and proximal tubular basement membrane in adult thin basement membrane disease

Nishi, Shinichi; Ueno, Mituhiro; Karasawa, Ryo; Kawashima, Shinji; In, Hian; Hayashi, Hiroshi; Saito, Noriko; Shimada, Hideaki; Yamazaki, Hajime; Imai, Naofumi; Gejyo, Fumitake; Arakawa, Masaaki

doi:10.1007/s101570050049

Cited by 2 publications

(2 citation statements)

References 25 publications

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“…The general increase in basement membrane proteins is likely due to the increase in total basement membrane volume as shown in 3D for COL4 and HSPG2 (Supplemental Figures 10 and 11, Supplemental Videos 1 and 2), and the previously described increase in thickness with age. [83][84][85] This change in geometry could be a physiologic response to increasing hydrostatic pressure and urine output with development. 51,86 COL4 and HSPG2 are necessary for basement membrane integrity, because mutations can lead to tubular basement membrane splitting and cysts, glomerulocystic disease, and altered functioning of the glomerular basement membrane.…”

Section: Discussionmentioning

confidence: 99%

3D Mapping Reveals a Complex and Transient Interstitial Matrix During Murine Kidney Development

Lipp

Jacobson

Schwarderer

et al. 2021

JASN

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BackgroundThe extracellular matrix (ECM) is a network of proteins and glycosaminoglycans that provides structural and biochemical cues to cells. In the kidney, the ECM is critical for nephrogenesis; however, the dynamics of ECM composition and how it relates to 3D structure during development is unknown.MethodsUsing embryonic day 14.5 (E14.5), E18.5, postnatal day 3 (P3), and adult kidneys, we fractionated proteins based on differential solubilities, performed liquid chromatography–tandem mass spectrometry, and identified changes in ECM protein content (matrisome). Decellularized kidneys were stained for ECM proteins and imaged in 3D using confocal microscopy.ResultsWe observed an increase in interstitial ECM that connects the stromal mesenchyme to the basement membrane (TNXB, COL6A1, COL6A2, COL6A3) between the embryo and adult, and a transient elevation of interstitial matrix proteins (COL5A2, COL12A1, COL26A1, ELN, EMID1, FBN1, LTBP4, THSD4) at perinatal time points. Basement membrane proteins critical for metanephric induction (FRAS1, FREM2) were highest in abundance in the embryo, whereas proteins necessary for integrity of the glomerular basement membrane (COL4A3, COL4A4, COL4A5, LAMB2) were more abundant in the adult. 3D visualization revealed a complex interstitial matrix that dramatically changed over development, including the perinatal formation of fibrillar structures that appear to support the medullary rays.ConclusionBy correlating 3D ECM spatiotemporal organization with global protein abundance, we revealed novel changes in the interstitial matrix during kidney development. This new information regarding the ECM in developing kidneys offers the potential to inform the design of regenerative scaffolds that can guide nephrogenesis in vitro.

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Section: Discussionmentioning

confidence: 99%

3D Mapping Reveals a Complex and Transient Interstitial Matrix During Murine Kidney Development

Lipp

Jacobson

Schwarderer

et al. 2021

JASN

View full text Add to dashboard Cite

show abstract

“…The general increase in basement membrane proteins (AGRN, COL4A1, COL4A2, HSPG2, LAMA1, LAMA4, LAMB1, LAMC1, NID1, NID2, TINAG, and TINAGL1) is likely due to the increase in total basement membrane volume as shown in 3D for COL4A1 and HSPG2 ( Figures 5, 7, S6, S7; Videos S1, S2), as well as the previously described increase in thickness with age. [78][79][80] This change in geometry could be a physiological response to increasing hydrostatic pressure and urine output over the course of development. 46,81 COL4A1 and HSPG2 are necessary for basement membrane integrity as mutations can lead to tubular basement membrane splitting and cysts, glomerulocystic disease, and altered GBM function.…”

Section: Discussionmentioning

confidence: 99%

3D mapping reveals a complex and transient interstitial matrix during murine renal development

Lipp

Jacobson

Schwarderer

et al. 2020

Preprint

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Background: The extracellular matrix (ECM) is a network of proteins and glycosaminoglycans that provides structural and biochemical cues to cells. In the kidney, the ECM is critical for nephrogenesis; however, the dynamics of ECM composition and how it relates to 3D structure during development is unknown. Methods: Using embryonic day (E)14.5, E18.5, postnatal day (P)3, and adult kidneys, we fractionated proteins based on differential solubilities, performed liquid chromatography tandem-mass spectrometry, and identified changes in ECM protein content (matrisome). Decellularized kidneys were stained for ECM proteins and imaged in 3D using confocal microscopy. Results: We observed an increase in interstitial ECM that connect the stromal mesenchyme to the basement membrane (TNXB, COL6A1, COL6A2, COL6A3) between the embryo and adult, and a transient elevation of interstitial matrix proteins (COL5A2, COL12A1, COL26A1, ELN, EMID1, FBN1, LTBP4, THSD4) at perinatal timepoints. Basement membrane proteins critical for metanephric induction (FRAS1, FREM2) were highest in the embryo, whereas proteins necessary for glomerular basement membrane integrity (COL4A3, COL4A4, COL4A5, LAMB2) were more abundant in the adult. 3D visualization revealed a complex interstitial matrix that dramatically changed over development, including the perinatal formation of fibrillar structures that appear to support the medullary rays. Conclusion: By correlating 3D ECM spatiotemporal organization with global protein abundance, we identified novel changes in the interstitial matrix during kidney development. This new information regarding the ECM in developing kidneys offers the potential to inform the design of regenerative scaffolds that can guide nephrogenesis in vitro.

show abstract

Morphometric study of glomerular basement membrane and proximal tubular basement membrane in adult thin basement membrane disease

Cited by 2 publications

References 25 publications

3D Mapping Reveals a Complex and Transient Interstitial Matrix During Murine Kidney Development

3D Mapping Reveals a Complex and Transient Interstitial Matrix During Murine Kidney Development

3D mapping reveals a complex and transient interstitial matrix during murine renal development

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